WO2007095716A1 - Compositions and methods for the induction and maintenance of quality sleep - Google Patents

Compositions and methods for the induction and maintenance of quality sleep Download PDF

Info

Publication number
WO2007095716A1
WO2007095716A1 PCT/CA2006/001156 CA2006001156W WO2007095716A1 WO 2007095716 A1 WO2007095716 A1 WO 2007095716A1 CA 2006001156 W CA2006001156 W CA 2006001156W WO 2007095716 A1 WO2007095716 A1 WO 2007095716A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
extract
sleep
melatonin
per serving
Prior art date
Application number
PCT/CA2006/001156
Other languages
French (fr)
Inventor
Marvin Heuer
Shan Chaudhuri
Ken Clement
Original Assignee
Iomedix Sleep International Srl
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Iomedix Sleep International Srl filed Critical Iomedix Sleep International Srl
Priority to CA002642761A priority Critical patent/CA2642761A1/en
Priority to JP2008555578A priority patent/JP2009527504A/en
Priority to EP06761118A priority patent/EP1991241A4/en
Priority to AU2006338839A priority patent/AU2006338839A1/en
Publication of WO2007095716A1 publication Critical patent/WO2007095716A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539—Scutellaria (skullcap)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/76—Salicaceae (Willow family), e.g. poplar
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/84—Valerianaceae (Valerian family), e.g. valerian
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/02—Nutrients, e.g. vitamins, minerals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00—Semiconductor devices specially adapted for rectifying, amplifying, oscillating or switching and having potential barriers; Capacitors or resistors having potential barriers, e.g. a PN-junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
    • H01L29/40—Electrodes ; Multistep manufacturing processes therefor
    • H01L29/401—Multistep manufacturing processes
    • H01L29/4011—Multistep manufacturing processes for data storage electrodes
    • H01L29/40114—Multistep manufacturing processes for data storage electrodes the electrodes comprising a conductor-insulator-conductor-insulator-semiconductor structure
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00—Semiconductor devices specially adapted for rectifying, amplifying, oscillating or switching and having potential barriers; Capacitors or resistors having potential barriers, e.g. a PN-junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
    • H01L29/40—Electrodes ; Multistep manufacturing processes therefor
    • H01L29/41—Electrodes ; Multistep manufacturing processes therefor characterised by their shape, relative sizes or dispositions
    • H01L29/423—Electrodes ; Multistep manufacturing processes therefor characterised by their shape, relative sizes or dispositions not carrying the current to be rectified, amplified or switched
    • H01L29/42312—Gate electrodes for field effect devices
    • H01L29/42316—Gate electrodes for field effect devices for field-effect transistors
    • H01L29/4232—Gate electrodes for field effect devices for field-effect transistors with insulated gate
    • H01L29/42324—Gate electrodes for transistors with a floating gate
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00—Semiconductor devices specially adapted for rectifying, amplifying, oscillating or switching and having potential barriers; Capacitors or resistors having potential barriers, e.g. a PN-junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
    • H01L29/66—Types of semiconductor device ; Multistep manufacturing processes therefor
    • H01L29/68—Types of semiconductor device ; Multistep manufacturing processes therefor controllable by only the electric current supplied, or only the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched
    • H01L29/76—Unipolar devices, e.g. field effect transistors
    • H01L29/772—Field effect transistors
    • H01L29/78—Field effect transistors with field effect produced by an insulated gate
    • H01L29/788—Field effect transistors with field effect produced by an insulated gate with floating gate
    • H01L29/7881—Programmable transistors with only two possible levels of programmation
    • H01L29/7884—Programmable transistors with only two possible levels of programmation charging by hot carrier injection
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L29/00—Semiconductor devices specially adapted for rectifying, amplifying, oscillating or switching and having potential barriers; Capacitors or resistors having potential barriers, e.g. a PN-junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
    • H01L29/66—Types of semiconductor device ; Multistep manufacturing processes therefor
    • H01L29/68—Types of semiconductor device ; Multistep manufacturing processes therefor controllable by only the electric current supplied, or only the electric potential applied, to an electrode which does not carry the current to be rectified, amplified or switched
    • H01L29/76—Unipolar devices, e.g. field effect transistors
    • H01L29/772—Field effect transistors
    • H01L29/78—Field effect transistors with field effect produced by an insulated gate
    • H01L29/788—Field effect transistors with field effect produced by an insulated gate with floating gate

Definitions

  • compositions and Methods for the Induction and Maintenance of Quality Sleep are Compositions and Methods for the Induction and Maintenance of Quality Sleep
  • the present invention relates to a composition to aid in the induction and maintenance of sleep in a user, e.g., human.
  • Sleep typically occupies about one-third of a person's life and affects a person's mental and physical well-being. It additionally affects mood, behavior and physiology. Sleep and the control of sleep is a complex process involving multiple chemicals and brain structures. It is a dynamic process involving distinct physiological changes and involves both positive and negative signaling.
  • the regulation of sleep in humans is governed by three processes - each influenced by hormonal and environmental factors: a daily sleep-wake cycle influenced by a circadian rhythm (24 hour cycle) tied to light-dark cycles controlled by a cluster of about 10,000 neurons located in the hypothalamus behind the eyes, called the suprachiasmatic nuclei (Hastings MH. Central clocking. Trends Neurosci. 1997
  • insomnia has been estimated to affect 40% of North Americans per year (Stoller MK. Economic effects of insomnia. Clin Then 1994 Sep-Oct;16(5):873-97).
  • GABA Gamma Aminobutyric Acid
  • the neurotransmitter Gamma Aminobutyric Acid (GABA) is a primary inhibitory neurotransmitter.
  • GABA- receptors are associated with chloride ion channels - signaling through the GABA-receptor changes the electrochemical gradient of the neuron, leading to activity inhibition (Olsen RW, Tobin AJ. Molecular biology of GABAA receptors. FASEB J. 1990 Mar;4(5): 1469-80).
  • Benzodiazepines are thought to act via interaction with the GABA receptor; enhancing the inhibitory effects of GABA.
  • Benzodiazepines are a widely used class of drugs primarily used as tranquilizers, muscle-relaxants, hypnotics or sedatives (Valenstein M, Taylor KK, Austin K, Kales HC, McCarthy JF, Blow FC. Benzodiazepine use among depressed patients treated in mental health settings. Am J Psychiatry. 2004 Apr;161(4):654-61.).
  • Adenosine may induce sleep by extracellular accumulation in specific brain regions such as the basal forebrain during prolonged wakefulness (Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Portas CM, Greene RW, McCarley RW.
  • Basal forebrain during prolonged wakefulness
  • Basheer R Basheer R
  • Dauphin LJ Rannie DG
  • Portas CM Greene RW
  • McCarley RW McCarley RW.
  • adenosine A1 receptor Thakkar MM, Winston S, McCarley RW. A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain. J Neurosci. 2003 May 15;23(10):4278-87.) can lead to the induction and maintenance of sleep.
  • the stimulatory effects of caffeine are thought to be due to antagonism of adenosine
  • A1 receptors (Sawynok J. Pharmacological rationale for the clinical use of caffeine. Drugs. 1995 Jan;49(1 ):37-50.), wherein an aroused state is observed.
  • Melatonin Another chemical associated with sleep is Melatonin. It is a hormone produced by the pineal gland from the amino acid tryptophan. Production is rhythmic in keeping with an intrinsic cycle of approximately 24-hours in duration, wherein levels are low during the day and increasing towards the nighttime (Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20- h day. Am J Physiol. 1999 Oct;277(4 Pt 2):R1152-63).
  • Melatonin appears to have two distinct effects on the circadian clock: neuronal inhibition and phase- shifting of the sleep cycle (Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, Reppert SM. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997 Jul;19(1 ):91- 102.). Oral administration of supplemental melatonin during the day induces sleepiness and improves night sleep (Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH.
  • Serotonin (5-hydroxytryptamine, 5HT), like melatonin, also displays a diurnal pattern; however, it functions in an opposing rhythm with daytime levels being higher than nighttime levels Portas CM, Bjorvatn B, Fagerland S, Gronli J, Mundal V, Sorensen E, Ursin R. On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience. 1998 Apr;83(3):807-1.). Three basic serotonin receptor types have been identified: 5HT-1 , 5HT-2 and 5HT-3. Several subtypes of 5HT-1 have also been identified.
  • Serotonin has been shown to inhibit GABA receptors (Feng J, Cai X, Zhao J, Yan Z. Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons. J Neurosci. 2001 Sep 1;21(17):6502-11.), likely contributing to the opposing actions of serotonin and GABA and play a role in sleep.
  • the present invention provides for a composition directed towards the induction of sleep. More specifically, the invention is directed towards a sleep-promoting and pain-relief composition.
  • the sleep-promoting and pain-relief composition of the present invention may additionally provide for maintenance of sleep, thereby promoting a good quality, restful sleep as well as alleviating minor aches and pains, thus further improving the quality of the person's sleep.
  • the composition of the present invention comprises an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
  • the present invention may be effective in promoting a restful night's sleep by speedily inducing a person to fall asleep and maintain sleep as well as alleviating minor aches and pains further improving the quality of an individual's, e.g. a human or animal, sleep.
  • the present invention advantageously provides a method for the maintenance of sleep thereby promoting a good quality, restful sleep as well as alleviating minor aches and pains, thus further improving the quality of an individual's, e.g. human or animal, sleep by administering to a human or a animal a composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
  • the present invention may provide a composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
  • the composition may include one or more of an extract of Hops cone, Lavender flower powder, an extract of Passionflower, Skullcap powder, an extract of Coenzyme Q10, a leaf of extract Lemon Balm.
  • the composition may include a time-release mechanism, e.g., wherein the time-release mechanism provides 4 hours of active compound release.
  • the melatonin may be incorporated into a tablet coating to promote sleep more quickly, e.g., to promote instant or immediate sleep.
  • all or a portion of the melatonin may be fine-milled.
  • the extract of Valerian Root, the extract of Willow Bark and the Melatonin or a derivative thereof are provided in amounts effective to at least one of promote sleep and relieve pain.
  • the present invention is advantageously directed towards a sleep-promoting and pain-relief composition which, for example, may induce sleep and promote the maintenance of sleep leading to a restful night's sleep, as well as alleviate minor aches and pains, further improving the quality of a person's sleep.
  • a sleep-promoting and pain-relief composition which, for example, may induce sleep and promote the maintenance of sleep leading to a restful night's sleep, as well as alleviate minor aches and pains, further improving the quality of a person's sleep.
  • Compounds employed in various embodiments of the present invention have been shown to be active at receptor sites in the central nervous system that relate to the induction and maintenance of sleep.
  • the composition of the present invention also contains compounds shown to alleviate minor aches and pains.
  • the present invention may include the use of combinations, wherein the combination includes, without being limited to, one or more of the following: Melatonin, Coenzyme Q10, Lemon Balm leaf extract, Hops cone extract, Lavender flower extract, Passionflower extract, Skullcap, deodorized Valerian root and Willow bark extract.
  • the supplement may be consumed in any form, e.g., a capsule, a tablet, a caplet, a liquid beverage, a powder beverage mix, or as a dietary gel.
  • the preferred dosage form of the present embodiment is a timed release caplet.
  • the dosage form of the diet supplement in accordance with the example embodiment set forth below, may be provided in accordance with customary processing techniques for herbal and/or dietary supplements, wherein the active ingredients are suitably processed into a desired form.
  • one or more ingredients of the diet supplement are processed so as to form fine-milled particles.
  • one or more ingredients of the supplemental dietary composition is processed by a large-scale dry milling technique that produces fine particles, preferably known as fine-milled particles.
  • Fine-milled particles have been shown to improve flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties.
  • Formulations may benefit by containing fine-milled particles because providing one or more ingredients in fine-milled particle sizes may optimize one or more of the flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties of the one or more ingredients in a diet supplement.
  • In vitro tests designed to simulate the environment of a stomach were performed to test the dissolution rate of fine-milled particle tablets relative to tablets having particles that are not fine-milled.
  • the supplemental composition contains fine-milled particles having an average size between about 2 nm and about 50 nm.
  • U.S. Provisional Patent Application 60/776,325 discloses a method for improving the absorption, palatability, taste, texture, and bioavailability of compounds by increasing the solubility of compounds in proprietary formulations for the purposes of enhancing or improving muscle size, growth and/or recovery time and/or weight loss.
  • the increased bioavailability of the compound or ingredients is achieved by reducing the particle size via "fine-milling" thereby increasing the surface area-to-volume ratio of each particle, thus increasing the rate of dissolution.
  • the compositions and methods disclosed promote increased bioavailability by increasing the total surface area of poorly soluble particles, thereby increasing the rate of absorption.
  • fine-milled and/or fine-milling refers to the process of micronization.
  • Micronization is a mechanical process that involves the application of force to a particle, thereby resulting in a reduction in the size of the particle.
  • the force in the case of micronization, may be applied in any manner such as, e.g., the collision of particles at high rates of speed, grinding, or by an air-jet micronizer.
  • fine-milled particles are obtained by jet-milling with nitrogen and compressed air.
  • particle size refers to the diameter of the particle.
  • average particle size means that at least 50% of the particles in a sample will have the specified particle size.
  • at least 80% of the particles in a sample will have the specified particle size, and more preferably, at least 90% of the particles in a given sample will have the specified particle size.
  • the size of a particle can be determined by any of the methods known within the art. Methods for particle size determination which may be employed are, e.g., sieves, sedimentation, electrozone sensing (Coulter counter), microscopy, and/or Low Angle Laser Light Scattering.
  • the preferred methods for the particle size determination of the present invention are the methods which are most commonly used in the pharmaceutical industry, such as laser diffraction, e.g., via light scattering Coulter Delsa 440SX.
  • the fine-milling process may be employed in the processing of one or more of the ingredients of the present invention in the dosage forms of tablets
  • capsules e.g., immediate-release and modified-release
  • liquid dispersions powders, drink mixes, etc.
  • the dosage form of the nutritional supplement in accordance with the aforementioned embodiment or further embodiments as interpreted by one of skill in the art related to the present invention may be provided in accordance with customary processing techniques for herbal and/or dietary and/or nutritional supplements in any of the forms mentioned above.
  • Melatonin is a hormone produced by the pineal gland from tryptophan and is involved in sleep regulation (Reiter RJ. melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991 May;12(2):151-80.). It is used to treat sleep disorders such as insomnia and 'jet lag' by stimulating the release of specific pituitary hormones (Ninomiya T, Iwatani N, Tomoda A, Miike T. Effects of exogenous melatonin on pituitary hormones in humans. Clin Physiol. 2001 May;21(3):292-9.) and adjusting the circadian rhythm to coincide with the local day and nighttime.
  • Melatonin supplementation has been demonstrated to be safe and effective at increasing the total amount of sleep time in healthy subjects (Matsumoto M. The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry Clin Neurosci. 1999 Apr;53(2):243-5.). Moreover, Melatonin has also been shown to benefit individuals suffering from insomnia (Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep.
  • Melatonin may also normalize the circadian rhythm and benefit shift workers and individuals with circadian rhythm disorders (Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med. 1998 Feb;30(1 ):122-30.; Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004 Jan;89(1 ): 128-34.; Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC. Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep. 2005 Oct 1;28(10):1271-8.).
  • Melatonin may also been shown to be effective in treating seasonal depression (Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res. 1998 Jan 16;77(1):57-61.) and migraines (Peres MF, Zukerman E, da Cunha Tanuri F, Moreira FR, Cipolla-Neto J. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757.).
  • One aspect of the present invention includes the use of Melatonin for the regulation of sleep.
  • U.S. Patent Nos. 6,703,412, 5,716,978, and 5,641 ,801 disclose methods of treating sleeplessness, sleep latency period, circadian rhythm disorders involving Melatonin.
  • U.S. Patent No. 6,703,412 entitled “Method of Treating Sleeplessness with Melatonin on an Acute Basis” purports to describe a method of treating sleeplessness in a human comprising the administration of an effective amount of not greater than 10 mg of melatonin or a pharmaceutically acceptable salt thereof.
  • the method further comprises the administration of melatonin after a person has tried and failed to go to sleep, or has awakened from sleep and is unable to return to sleep.
  • the method may be employed up to one hour from the person's desired waking time.
  • U.S. Patent No. 5,716,978, entitled “Methods of Treating Circadian Rhythm Disorders” describes a method in which infants and blind humans employ the administration of Melatonin to produce a phase-shifting effect and reinstate a proper circadian rhythm.
  • the method involves the administration of Melatonin from about 6 hours to about 19 hours prior to when a normal sleep phase should begin.
  • the administration of Melatonin is to be less than 1 mg and at a time prior to a person's endogenous Melatonin onset time.
  • the supplemental composition may include Melatonin.
  • a serving of the supplemental composition may include from about 0.001 g to about 0.01 g of Melatonin.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0040 g of Melatonin.
  • the supplemental composition may include fine-milled Melatonin.
  • a serving of the supplemental composition may include from about 0.0001 g to about 0.01 g of fine-milled Melatonin.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of fine-milled Melatonin.
  • Coenzyme Q10 (CoQIO, ubiquinone) is found in the mitochondria of all cells and is involved in energy production. It is found at its highest concentrations in the heart, liver, kidney and pancreas. CoQIO is a potent antioxidant in human blood (Weber C, Sejersgard Jakobsen T, Mortensen SA, Paulsen G, Holmer G. Antioxidative effect of dietary coenzyme Q10 in human blood plasma., lnt J Vitam Nutr Res. 1994;64(4):311-5.) where it also acts to preserve vitamin E, another major antioxidant (Thomas SR, Neuzil J, Stacker R. Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme Q in atherogenesis? MoI Aspects Med. 1997;18 Suppl:S85-103).
  • CoQ 10 Due to its high concentrations in the heart, CoQ 10 is believed to benefit and strengthen the heart. Many heart-related diseases are thought to result from defective myocardial energy production and numerous studies have suggested that supplementation with CoQIO is beneficial (Mortensen SA. Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). Clin Investig. 1993,71(8 Suppl):S116-23.). A meta-analysis of eight clinical trials supports the efficacy of CoQIO for the treatment of congestive heart failure (Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials. MoI Aspects Med. 1997;18 Suppl:S159-68.).
  • CoQIO in a phase Il clinical trial was reported to slow the progression of Parkinson's disease (Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol.
  • CoQ10 has been successfully used to treat high blood pressure, eliminating the need for medication in many cases (Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. MoI Aspects Med. 1994;15 Suppl:S265-72.).
  • Migraines have also been successfully and safely treated with CoQIO (Sandor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005 Feb 22;64(4):713-5.) most likely due its effects on blood pressure.
  • CoQIO Sandor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J.
  • CoQIO was shown to provide relieve from snoring in about half of the subjects, displaying a decrease in the sound level of their snoring (Takasaki Y, Yoshida H, Kaneko Y, Kaneda R, Kurosaki S, Yamadera Y., An Analysis of Effectiveness of Activated Co-enzyme Q10 on Subjects by Using Acoustic Technology. Biopharma Ltd. Tokyo Japan).
  • the supplemental composition may include CoEnzyme Q10.
  • a serving of the supplemental composition may include from about 0.0005 g to about 0.1000 g of CoEnzyme Q10.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of CoEnzyme Q 10.
  • Lemon Balm Leaf Extract The plant Melissa officinalis, commonly known as Lemon balm is a member of the mint family and is often referred to as 'the calming herb”. Lemon balm extract has proven antioxidant activity which likely contributes to its beneficial effects (Hohmann J, Zupko I, Redei D, Csanyi M, Falkay G, Mathe I, Janicsak G.
  • Lemon balm extract (Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6.).
  • the treatment group also displayed less agitation than the placebo group, suggesting an improvement in mood.
  • Clinical trials have demonstrated that Lemon balm can be effective at reducing stress and anxiety when used in combination with Valeriana (Kennedy DO, Little W, Haskell CF, Scholey AB.
  • the supplemental composition may include Lemon Balm leaf extract.
  • a serving of the supplemental composition may include from about 0.0010 g to about 0.1000 g of Lemon Balm leaf extract.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0800 g of Lemon Balm leaf extract.
  • Hops cone extract Humulus lupulus
  • the hop plant (Humulus lupulus) is a flowering vine used traditionally as a sedative to assist with anxiety reduction and sleep difficulties. In mice, hops extract displays sleep-enhancing and antidepressant activities (Zanoli P, Rivasi
  • hops contain compounds with antioxidant and chemoprotective activity as well as compounds that can induce detoxification enzymes (Dietz BM, Kang YH, Liu G, Eggler AL, Yao P, Chadwick LR, Pauli GF, Farnsworth NR, Mesecar AD, van Breemen RB, Bolton JL. Xanthohumol isolated from Humulus lupulus Inhibits menadione-induced DNA damage through induction of quinone reductase. Chem Res Toxicol. 2005 Aug;18(8):1296-305.).
  • valerian and hops have been shown to interact with adenosine receptors (Muller CE, Schumacher B, Brattstrom A, Abourashed EA,
  • hop extract has been shown to modulate the gamma-aminobutyric acid receptor (GABA(A) receptors) and display GABA-like activity (Aoshima H, Takeda K, Okita Y, Hossain SJ, Koda H, Kiso Y. Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors. J Agric Food Chem. 2006 Apr 5;54(7):2514- 9.) relating to sleep.
  • GABA is an inhibitory neurotransmitter that can induce relaxation and sleep. Modulation of any or all of these receptors may mediate the sleep-inducing activity of hops.
  • the supplemental composition may include Hops cone extract.
  • a serving of the supplemental composition may include from about 0.0010 g to about 0.1000 g of Hops cone extract.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0200 g of Hops cone extract.
  • Lavender Flower Oil from Lavandula officinalis, commonly known as the Lavender plant is frequently used in aromatherapy as a mode to induce relaxation.
  • the mild sedative effects of Lavender have been demonstrated in animals and humans (Lis-Balchin M, Hart S. Studies on the mode of action of the essential oil of lavender (Lavandula angustifolia P. Miller). Phytother Res. 1999 Sep;13(6):540- 2.). Further to the sedative effect, Lavender oil has been shown to reduce agitation of patients suffering from dementia (Holmes C, Hopkins V, Hensford C, MacLaughlin V, Wilkinson D, Rosenvinge H.
  • Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study, lnt J Geriatr Psychiatry. 2002 Apr;17(4):305-8.). Moreover, Lavender has also been shown be beneficial for treating depression (Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S, Mobaseri M, Moin M, Khani M, Jamshidi AH, Baghalian K, Taghizadeh M. Comparison of Lavandula angustifolia Mill, tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1 ):123-7.).
  • the supplemental composition may include Lavender Flower powder.
  • a serving of the supplemental composition may include from about 0.0010 g to about 0.0100 g of Lavender Flower powder.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0050 g of Lavender Flower powder.
  • Passion flower has been used traditionally for relaxation and as a sleep- aid as well as a treatment for anxiety.
  • the main active component of Passionflower is thought to by chrysin, one of several flavonoids which have been isolated from this plant (Menghini A, Mancini LA. TLC determination of flavonoid accumulation in clonal populations of Passiflora incarnata L. Pharmacol Res Commun. 1988 Dec;20 Suppl 5:113-6.; Pereira CA, Yariwake JH, Lancas FM, Wauters JN, Tits M, Angenot L. A HPTLC densitometric determination of flavonoids from Passiflora alata, P. edulis, P. incarnata and P.
  • chrysin has been shown to act as an agonist of benzodiazepine receptors and also possess anti-anxiety activity (Wolfman C, Viola H, Paladini A, Dajas F, Medina JH. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav. 1994 Jan;47(1 ):1-4.).
  • One aspect of the present invention includes the use of Passionflower extract for the reduction of stress and anxiety.
  • U.S. Patent Nos. 6,080,410 and 5,681 ,578 describe a method and composition, respectively, employing Passionflower extracts for the reduction of stress and anxiety.
  • U.S. Patent No. 6,080,410 entitled “Method for Reducing Daily Stress and Anxiety in Adults,” describes a method of employing a novel dietary supplement which serves a general relaxant comprised of Kava root extract, and at least one of Passionflower, Chamomile Flower, Hops, and Schizandra Fruit. The method claims to reduce daily stress and anxiety in adults. It is administered in capsule format.
  • Aminobutyric acid glutamine, glycine, magnesium, passionflower, primal officinalis and vitamin B6.
  • the composition is purported to relieve stress, anxiety, grief and depression.
  • the supplemental composition may include Passionflower extract.
  • a serving of the supplemental composition may include from about 0.0010 g to about 0.0100 g of Passionflower extract.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0020 g of Passionflower extract.
  • Scutellaria also known commonly as Skullcap
  • Skullcap is a member of the mint family and has been used traditionally to treat depression and stress.
  • Studies in mice indicate that Skullcap reduces anxiety (Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z.
  • Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003 Nov;10(8):640-9.).
  • the effects of Skullcap may be at least partially mediated by antagonism of serotonin receptors (Gafner S, Bergeron C, Batcha LL, Reich J, Arnason JT, Burdette JE, Pezzuto JM, Angerhofer CK. Inhibition of [3H]-LSD binding to 5-HT7 receptors by flavonoids from Scutellaria lateriflora. J Nat Prod. 2003 Apr;66(4):535-7.).
  • a clinical study involving healthy volunteers also demonstrated that Skullcap reduces anxiety (Wolfson P, Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. Altern Ther Health Med. 2003 Mar-Apr;9(2):74- 8.).
  • U.S. Patent No. 7,045,158 entitled “Standardized Extracts of Scutellaria Laterifloa,” describes an improved extract of Scutellaria Laterifloa and relates to a pharmaceutical composition prepared from said extract wherein it is suitable for treating anxiety, insomnia, convulsions, muscle tension and spasms.
  • the supplemental composition may include Skullcap powder.
  • a serving of the supplemental composition may include from about 0.0001 g to about 0.0100 g of Skullcap powder.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of Skullcap powder.
  • Valerian Root (Valeriana officinalis) Valeriana officinalis, wherein the root, normally called Valerian root, is a perennial herb traditionally used as a sedative and sleep-aid.
  • Compounds from Valerian interact with GABA, melatonin, and/or adenosine systems through binding to certain melatonin and serotonin receptor subtypes (Abourashed EA, Koetter U, Brattstrom A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004 Nov;11(7-8):633-8.), particularly the 5-HT 5A subtype (Dietz BM, Mahady GB, Pauli GF, Famsworth NR. Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res MoI Brain Res. 2005 Aug 18;138(2):191-7.). Interaction with this receptor is thought to be responsible for the sleep-inducing and maintenance effect of Valerian root extract.
  • Valerian root extract has proven to be useful in several clinical trials. Subjective self-evaluation of sleep quality improved in a valerian supplemented group as part of a randomized controlled trial (Leathwood PD, Chauffard F 1 Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav. 1982 JuI; 17(1 ):65- 71.), compared to control groups. In another clinical trial, the valerian group reported improved sleep over the placebo group, with 89% of participants reporting improved sleep (Lindahl O, Lindwall L. Double blind study of a valerian preparation. Pharmacol Biochem Behav. 1989 Apr;32(4): 1065-6.).
  • One aspect of the present invention includes the use of Valerian for improving the quality of sleep and reducing minor aches and pains.
  • U.S. Patent Nos. 6,869,622 and 6,383,527 describe respective compositions for improving the quality of sleep and alleviating muscular aches and strains, particularly with respect to those in the lower back.
  • U.S. Patent No. 6,869,622 entitled “Composition for Improving Sleep Quality and Efficiency, And Method of Preparing and Using the Composition,” describes a pharmaceutically active extract of the plant root family of Valerianaceae and its usefulness in improving sleep quality and efficiency.
  • the patent purports to relate to a method for reducing the number of times a patient wakes after sleep onset, comprising administering to the patient a pharmaceutically-active extract of the root of a plant of the family Valerianaceae, wherein it is processed via an ethanolic and water extraction.
  • a single dosage is administered between the range of 50 mg and 5000 mg approximately one-half and two hours prior to bedtime.
  • the supplemental composition may include Valerian Root.
  • a serving of the supplemental composition may include from about 0.1000 g to about 1.000 g of Valerian Root.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.1200 g of Valerian Root.
  • Willow bark extract providing salicin
  • Salix alba 25% salicin Willow bark (Salix alba) is a source of salicin, a precursor of acetylsalicylic acid (aspirin) traditionally used to treat pain, fever and inflammation.
  • One aspect of the present invention includes the use of Willow bark for the attenuation of minor aches and pains, leading to an improved quality of sleep.
  • U.S. Patent Nos. 6,770,263 and 6,312,736 describe compositions for the treatment, e.g., alleviation, of aches and pains.
  • compositions and Methods for the Treatment of Aches and Pains purports to describe methods and compositions useful for treating aches and/or pains.
  • the composition comprises an aqueous medium having dispersed or dissolved therein an analgesic selected from the group consisting of white willow bark, aspirin, ibuprofen, naproxen, and any combination thereof.
  • the composition is then administered in an effective amount across a mucosal membrane.
  • U.S. Patent No. 6,312,736, entitled “Herbal Composition to Relieve Pain,” describes a composition used to relieve pain and other symptoms associated with migraines and other types of headaches.
  • the composition comprises a combination of White Willow bark extract, Kava Kava root extract, Feverfew extract, Ginger root extract, Guarana extract, and Vitamin B6 wherein the composition may be combined with liposomes to carry the composition in a sublingual dosage for fast pain relief.
  • the supplemental composition may include Willow bark extract.
  • a serving of the supplemental composition may include from about 0.1000 g to about 1.000 g of Willow bark extract.
  • the preferred dosage of a serving of the supplemental composition comprises about 0.1500 g Willow bark extract.
  • the present invention provides a method which includes the step of consuming a composition, wherein the method may, for example, alleviate minor aches and pains, speedily induce sleep, as well as provide for maintenance of sleep thereby promoting a good quality, restful sleep.
  • the method includes the daily consumption, prior to going to sleep with the intent of a full night's sleep, of a sleep-promoting and pain-relief composition that may include at least an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
  • the sleep-promoting and pain-relief composition may further comprise Coenzyme Q 10, Lemon Balm leaf extract, Hops cone extract, Lavender flower extract, Passionflower extract, and Skullcap powder.
  • the present supplemental composition may be utilized in methods to alleviate minor aches and pains, speedily induce sleep, as well as provide for maintenance of sleep thereby promoting a good quality, restful sleep in a formulation designed to be consumed on a daily basis prior to going to sleep with the intent of a night's rest.
  • the composition may include a time-release mechanism, e.g., wherein the time-release mechanism provides 4 hours of active compound release.
  • the melatonin may be incorporated into a tablet coating to promote sleep more quickly, e.g., to promote instant or immediate sleep.
  • a supplemental composition is provided on a daily basis, prior to going to sleep with the intent on a full night's rest, the composition utilizing a dual-release caplet formulation comprising Melatonin (0.0040 g), fine-milled Melatonin (0.0010 g), Coenzyme Q10 (0.0010 g), Hops cone extract (0.0200 g), Lavender flower powder (0.0050 g), Passionflower extract (0.0020 g), Skullcap powder (0.0010 g), Lemon Balm leaf extract (0.0800 g), deodorized Valerian root (0.1200 g) and Willow bark extract (0.1500 g).
  • Melatonin 0.0040 g
  • fine-milled Melatonin 0.0010 g
  • Coenzyme Q10 0.0010 g
  • Hops cone extract 0.0200 g
  • Lavender flower powder 0.0050 g
  • Passionflower extract 0.0020 g
  • Skullcap powder 0.0010 g
  • Lemon Balm leaf extract 0.0800 g
  • 1 caplet is orally administered with an 8 oz. glass of water once daily prior to going to sleep.
  • the supplemental composition is consumed with the intent of a full night's sleep.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Biotechnology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Power Engineering (AREA)
  • Microelectronics & Electronic Packaging (AREA)
  • Polymers & Plastics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physics & Mathematics (AREA)
  • Computer Hardware Design (AREA)
  • General Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Ceramic Engineering (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Neurosurgery (AREA)
  • Manufacturing & Machinery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)

Abstract

Supplemental compositions, and methods for administering same to a user, are provided for promoting a restful night's sleep by speedily inducing a person to fall asleep and to maintain sleep, as well as alleviating minor aches and pains so as to further improve the quality of a person sleep. The supplemental composition may include at least an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof. The supplemental composition may be provided for consumption at least one time daily, e.g., prior to sleep.

Description

Compositions and Methods for the Induction and Maintenance of Quality Sleep
Field of the Invention
The present invention relates to a composition to aid in the induction and maintenance of sleep in a user, e.g., human.
Background of the Invention
Sleep typically occupies about one-third of a person's life and affects a person's mental and physical well-being. It additionally affects mood, behavior and physiology. Sleep and the control of sleep is a complex process involving multiple chemicals and brain structures. It is a dynamic process involving distinct physiological changes and involves both positive and negative signaling. The regulation of sleep in humans is governed by three processes - each influenced by hormonal and environmental factors: a daily sleep-wake cycle influenced by a circadian rhythm (24 hour cycle) tied to light-dark cycles controlled by a cluster of about 10,000 neurons located in the hypothalamus behind the eyes, called the suprachiasmatic nuclei (Hastings MH. Central clocking. Trends Neurosci. 1997
Oct;20(10):459-64.); a separable oscillating sleep homeostatic process influenced by prior sleep (Dijk DJ, Lockley SW. Integration of human sleep-wake regulation and circadian rhythmicity. J Appl Physiol. 2002 Feb;92(2):852-62.); and an ultradian rhythm which occurs within the 24 hour circadian cycle.
The need for sleep is a biological drive similar to thirst or hunger. Interestingly though, the function of sleep is largely unknown, however some evidence indicates that sleep is required for learning (Stickgold R, James L, Hobson JA. Visual discrimination learning requires sleep after training. Nat Neurosci. 2000 Dec;3(12):1237-8.; Gais S, Plihal W, Wagner U, Born J. Early sleep triggers memory for early visual discrimination skills. Nat Neurosci. 2000 Dec;3(12): 1335-9.). Additionally, sleep deprivation studies in rats have shown that when rats are not allowed to sleep, the end-result is death apparently related to immune system failure (Everson CA. Sustained sleep deprivation impairs host defense. Am J Physiol. 1993 Nov;265(5 Pt 2):R1148-54.). In humans, similarly, mild sleep deprivation also results in indications of impaired immune system function (Irwin M, McClintick J, Costlow C, Fortner M, White J, Gillin JC. Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB J. 1996 Apr;10(5):643-53.). Although specific sleep requirements vary from individual to individual, sleeping less than six hours per day has been shown to increase the risk of glucose intolerance and diabetes (Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005 Apr 25;165(8):863-7.). Insomnia has been estimated to affect 40% of North Americans per year (Stoller MK. Economic effects of insomnia. Clin Then 1994 Sep-Oct;16(5):873-97). A study by the U.S. National Sleep Foundation and the Gallup Organization involving 1 ,000 randomly selected Americans revealed that insomnia negatively impacts activities during waking function and effects quality of life (Roth T, Ancoli-lsrael S. Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II. Sleep. 1999 May 1 ;22 Suppl 2.S354- 8.). Another study involving 261 insomnia sufferers and 101 individuals with no sleep complaints revealed that insomnia significantly impairs quality of life (Zammit GK, Weiner J, Damato N, Sillup GP, McMillan CA. Quality of life in people with insomnia. Sleep. 1999 May 1;22 Suppl 2:S379-85.).
The neurotransmitter Gamma Aminobutyric Acid (GABA) is a primary inhibitory neurotransmitter. One of its effects is to induce sleep. The GABA- receptors are associated with chloride ion channels - signaling through the GABA-receptor changes the electrochemical gradient of the neuron, leading to activity inhibition (Olsen RW, Tobin AJ. Molecular biology of GABAA receptors. FASEB J. 1990 Mar;4(5): 1469-80). Benzodiazepines are thought to act via interaction with the GABA receptor; enhancing the inhibitory effects of GABA. As such, Benzodiazepines are a widely used class of drugs primarily used as tranquilizers, muscle-relaxants, hypnotics or sedatives (Valenstein M, Taylor KK, Austin K, Kales HC, McCarthy JF, Blow FC. Benzodiazepine use among depressed patients treated in mental health settings. Am J Psychiatry. 2004 Apr;161(4):654-61.). Additionally, Adenosine, a neuromodulator, may induce sleep by extracellular accumulation in specific brain regions such as the basal forebrain during prolonged wakefulness (Strecker RE, Morairty S, Thakkar MM, Porkka-Heiskanen T, Basheer R, Dauphin LJ, Rainnie DG, Portas CM, Greene RW, McCarley RW. Adenosinergic modulation of basal forebrain and preoptic/anterior hypothalamic neuronal activity in the control of behavioral state. Behav Brain Res. 2000 Nov; 115(2): 183-204.; Zeitzer JM, Morales-Villagran A, Maidment NT, Behnke EJ, Ackerson LC, Lopez-Rodriguez F, Fried I, Engel J Jr, Wilson CL. Extracellular adenosine in the human brain during sleep and sleep deprivation: an in vivo microdialysis study. Sleep. 2006 Apr 1 ;29(4):455-61.). Actions on both the GABA-benzodiazepine receptor complex (Mendelson WB. Sleep-inducing effects of adenosine microinjections into the medial preoptic area are blocked by flumazenil. Brain Res. 2000 Jan 10;852(2):479-81.) and/or the adenosine A1 receptor (Thakkar MM, Winston S, McCarley RW. A1 receptor and adenosinergic homeostatic regulation of sleep-wakefulness: effects of antisense to the A1 receptor in the cholinergic basal forebrain. J Neurosci. 2003 May 15;23(10):4278-87.) can lead to the induction and maintenance of sleep. The stimulatory effects of caffeine are thought to be due to antagonism of adenosine
A1 receptors (Sawynok J. Pharmacological rationale for the clinical use of caffeine. Drugs. 1995 Jan;49(1 ):37-50.), wherein an aroused state is observed.
Another chemical associated with sleep is Melatonin. It is a hormone produced by the pineal gland from the amino acid tryptophan. Production is rhythmic in keeping with an intrinsic cycle of approximately 24-hours in duration, wherein levels are low during the day and increasing towards the nighttime (Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20- h day. Am J Physiol. 1999 Oct;277(4 Pt 2):R1152-63). Melatonin appears to have two distinct effects on the circadian clock: neuronal inhibition and phase- shifting of the sleep cycle (Liu C, Weaver DR, Jin X, Shearman LP, Pieschl RL, Gribkoff VK, Reppert SM. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997 Jul;19(1 ):91- 102.). Oral administration of supplemental melatonin during the day induces sleepiness and improves night sleep (Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci U S A. 1994 Mar 1 ;91(5):1824-8.). Two types of melatonin G- protein coupled receptors have been classified in mammals and termed MT1 and MT2 (Dubocovich ML, Markowska M. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine. 2005 Jul;27(2):101-10.). Serotonin (5-hydroxytryptamine, 5HT), like melatonin, also displays a diurnal pattern; however, it functions in an opposing rhythm with daytime levels being higher than nighttime levels Portas CM, Bjorvatn B, Fagerland S, Gronli J, Mundal V, Sorensen E, Ursin R. On-line detection of extracellular levels of serotonin in dorsal raphe nucleus and frontal cortex over the sleep/wake cycle in the freely moving rat. Neuroscience. 1998 Apr;83(3):807-1.). Three basic serotonin receptor types have been identified: 5HT-1 , 5HT-2 and 5HT-3. Several subtypes of 5HT-1 have also been identified. The exact response of cells to serotonin depends on the receptor types expressed (Andrade R. of membrane excitability in the central nervous system by serotonin receptor subtypes. Ann N Y Acad Sci. 1998 Dec 15;861 :190-203.) however, Serotonin has been shown to inhibit GABA receptors (Feng J, Cai X, Zhao J, Yan Z. Serotonin receptors modulate GABA(A) receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons. J Neurosci. 2001 Sep 1;21(17):6502-11.), likely contributing to the opposing actions of serotonin and GABA and play a role in sleep.
Summary of the Invention
The present invention according to one embodiment thereof, provides for a composition directed towards the induction of sleep. More specifically, the invention is directed towards a sleep-promoting and pain-relief composition. Advantageously, the sleep-promoting and pain-relief composition of the present invention may additionally provide for maintenance of sleep, thereby promoting a good quality, restful sleep as well as alleviating minor aches and pains, thus further improving the quality of the person's sleep. The composition of the present invention comprises an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof. For example, the present invention may be effective in promoting a restful night's sleep by speedily inducing a person to fall asleep and maintain sleep as well as alleviating minor aches and pains further improving the quality of an individual's, e.g. a human or animal, sleep. Furthermore, the present invention advantageously provides a method for the maintenance of sleep thereby promoting a good quality, restful sleep as well as alleviating minor aches and pains, thus further improving the quality of an individual's, e.g. human or animal, sleep by administering to a human or a animal a composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
According to an embodiment, the present invention may provide a composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof. Additionally, the composition may include one or more of an extract of Hops cone, Lavender flower powder, an extract of Passionflower, Skullcap powder, an extract of Coenzyme Q10, a leaf of extract Lemon Balm. The composition may include a time-release mechanism, e.g., wherein the time-release mechanism provides 4 hours of active compound release. Also, the melatonin may be incorporated into a tablet coating to promote sleep more quickly, e.g., to promote instant or immediate sleep. Also, in an embodiment of the present invention, all or a portion of the melatonin may be fine-milled. Advantageously, the extract of Valerian Root, the extract of Willow Bark and the Melatonin or a derivative thereof, are provided in amounts effective to at least one of promote sleep and relieve pain.
Detailed Description of the Invention
The present invention according to an embodiment thereof is advantageously directed towards a sleep-promoting and pain-relief composition which, for example, may induce sleep and promote the maintenance of sleep leading to a restful night's sleep, as well as alleviate minor aches and pains, further improving the quality of a person's sleep. Compounds employed in various embodiments of the present invention have been shown to be active at receptor sites in the central nervous system that relate to the induction and maintenance of sleep. Moreover, the composition of the present invention also contains compounds shown to alleviate minor aches and pains.
In an embodiment, the present invention may include the use of combinations, wherein the combination includes, without being limited to, one or more of the following: Melatonin, Coenzyme Q10, Lemon Balm leaf extract, Hops cone extract, Lavender flower extract, Passionflower extract, Skullcap, deodorized Valerian root and Willow bark extract. The supplement may be consumed in any form, e.g., a capsule, a tablet, a caplet, a liquid beverage, a powder beverage mix, or as a dietary gel. The preferred dosage form of the present embodiment is a timed release caplet.
As set forth above, the dosage form of the diet supplement, in accordance with the example embodiment set forth below, may be provided in accordance with customary processing techniques for herbal and/or dietary supplements, wherein the active ingredients are suitably processed into a desired form. In accordance with an embodiment of the present invention, one or more ingredients of the diet supplement are processed so as to form fine-milled particles. For instance, in an embodiment, one or more ingredients of the supplemental dietary composition is processed by a large-scale dry milling technique that produces fine particles, preferably known as fine-milled particles. The use of dry milling techniques, in combination with excipients and polymers, to form fine-milled particles has been shown to improve flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties. Formulations may benefit by containing fine-milled particles because providing one or more ingredients in fine-milled particle sizes may optimize one or more of the flow and dispersability, stability, resistance to moisture, bioavailability, and dissolution/release properties of the one or more ingredients in a diet supplement. In vitro tests designed to simulate the environment of a stomach were performed to test the dissolution rate of fine-milled particle tablets relative to tablets having particles that are not fine-milled. These test showed that in tablets produced from fine-milled particles the time to 100% dissolution was approximately 15 minutes. In the case of non-fine-milled particle compositions, only 90% dissolution was observed after 120 minutes. In a preferred embodiment, the supplemental composition contains fine-milled particles having an average size between about 2 nm and about 50 nm.
U.S. Provisional Patent Application 60/776,325 discloses a method for improving the absorption, palatability, taste, texture, and bioavailability of compounds by increasing the solubility of compounds in proprietary formulations for the purposes of enhancing or improving muscle size, growth and/or recovery time and/or weight loss. The increased bioavailability of the compound or ingredients is achieved by reducing the particle size via "fine-milling" thereby increasing the surface area-to-volume ratio of each particle, thus increasing the rate of dissolution. The compositions and methods disclosed promote increased bioavailability by increasing the total surface area of poorly soluble particles, thereby increasing the rate of absorption.
As used herein the, term "fine-milled" and/or "fine-milling" refers to the process of micronization. Micronization is a mechanical process that involves the application of force to a particle, thereby resulting in a reduction in the size of the particle. The force, in the case of micronization, may be applied in any manner such as, e.g., the collision of particles at high rates of speed, grinding, or by an air-jet micronizer. In a preferred embodiment, fine-milled particles are obtained by jet-milling with nitrogen and compressed air.
As used herein, the term "particle size" refers to the diameter of the particle. The term "average particle size" means that at least 50% of the particles in a sample will have the specified particle size. Preferably, at least 80% of the particles in a sample will have the specified particle size, and more preferably, at least 90% of the particles in a given sample will have the specified particle size.
The size of a particle can be determined by any of the methods known within the art. Methods for particle size determination which may be employed are, e.g., sieves, sedimentation, electrozone sensing (Coulter counter), microscopy, and/or Low Angle Laser Light Scattering. The preferred methods for the particle size determination of the present invention are the methods which are most commonly used in the pharmaceutical industry, such as laser diffraction, e.g., via light scattering Coulter Delsa 440SX.
The fine-milling process may be employed in the processing of one or more of the ingredients of the present invention in the dosage forms of tablets
(e.g., immediate-release film coated, modified-release and fast-dissolving), capsules (e.g., immediate-release and modified-release), liquid dispersions, powders, drink mixes, etc.
Furthermore, the dosage form of the nutritional supplement in accordance with the aforementioned embodiment or further embodiments as interpreted by one of skill in the art related to the present invention may be provided in accordance with customary processing techniques for herbal and/or dietary and/or nutritional supplements in any of the forms mentioned above. Melatonin
Melatonin is a hormone produced by the pineal gland from tryptophan and is involved in sleep regulation (Reiter RJ. melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev. 1991 May;12(2):151-80.). It is used to treat sleep disorders such as insomnia and 'jet lag' by stimulating the release of specific pituitary hormones (Ninomiya T, Iwatani N, Tomoda A, Miike T. Effects of exogenous melatonin on pituitary hormones in humans. Clin Physiol. 2001 May;21(3):292-9.) and adjusting the circadian rhythm to coincide with the local day and nighttime. Melatonin supplementation has been demonstrated to be safe and effective at increasing the total amount of sleep time in healthy subjects (Matsumoto M. The hypnotic effects of melatonin treatment on diurnal sleep in humans. Psychiatry Clin Neurosci. 1999 Apr;53(2):243-5.). Moreover, Melatonin has also been shown to benefit individuals suffering from insomnia (Hughes RJ, Sack RL, Lewy AJ. The role of melatonin and circadian phase in age-related sleep-maintenance insomnia: assessment in a clinical trial of melatonin replacement. Sleep. 1998;21(1 ):52-68.; Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30.; Brzezinski A, Vangel MG, Wurtman RJ, Norrie G, Zhdanova I, Ben-Shushan A, Ford I. Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev. 2005 Feb;9(1):41-50.) by way of the induction of sleep. The most common effect of melatonin on sleep is a reduction in sleep latency, the time taken to fall asleep (Zhdanova IV, Wurtman RJ, Lynch HJ, Ives JR, Dollins AB, Morabito C, Matheson JK, Schomer DL. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clin Pharmacol Ther. 1995 May;57(5):552-8.; Nagtegaal JE, Kerkhof GA, Smits MG, Swart AC, Van Der Meer YG. Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res. 1998 Jun;7(2):135-43.; Kayumov L, Brown G, Jindal R, Buttoo K, Shapiro CM. A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Psychosom Med. 2001 Jan-Feb;63(1 ):40-8.; Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Baker G, Klassen TP, Vohra S. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med. 2005 Dec;20(12):1151-8.), wherein it reduces the time it takes for an individual to fall asleep. Melatonin may also normalize the circadian rhythm and benefit shift workers and individuals with circadian rhythm disorders (Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med. 1998 Feb;30(1 ):122-30.; Kunz D, Mahlberg R, Muller C, Tilmann A, Bes F. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004 Jan;89(1 ): 128-34.; Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC. Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep. 2005 Oct 1;28(10):1271-8.).
Melatonin may also been shown to be effective in treating seasonal depression (Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psychiatry Res. 1998 Jan 16;77(1):57-61.) and migraines (Peres MF, Zukerman E, da Cunha Tanuri F, Moreira FR, Cipolla-Neto J. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757.). Furthermore, blood pressure as well as stress hormones can be reduced by daily oral administration of melatonin in healthy men (Arangino S, Cagnacci A, Angiolucci M, Vacca AM, Longu G, Volpe A, Melis GB. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol. 1999 May 1 ;83(9):1417-9.).
One aspect of the present invention includes the use of Melatonin for the regulation of sleep. U.S. Patent Nos. 6,703,412, 5,716,978, and 5,641 ,801 disclose methods of treating sleeplessness, sleep latency period, circadian rhythm disorders involving Melatonin.
For example, U.S. Patent No. 6,703,412, entitled "Method of Treating Sleeplessness with Melatonin on an Acute Basis" purports to describe a method of treating sleeplessness in a human comprising the administration of an effective amount of not greater than 10 mg of melatonin or a pharmaceutically acceptable salt thereof. The method further comprises the administration of melatonin after a person has tried and failed to go to sleep, or has awakened from sleep and is unable to return to sleep. The method may be employed up to one hour from the person's desired waking time.
U.S. Patent No. 5,716,978, entitled "Methods of Treating Circadian Rhythm Disorders" describes a method in which infants and blind humans employ the administration of Melatonin to produce a phase-shifting effect and reinstate a proper circadian rhythm. The method involves the administration of Melatonin from about 6 hours to about 19 hours prior to when a normal sleep phase should begin. The administration of Melatonin is to be less than 1 mg and at a time prior to a person's endogenous Melatonin onset time. U.S. Patent No. 5,641 ,801 entitled "Method of Reducing the Period before the Onset of Sleep" purports to describe a method of inducing sleep in an individual via the administration of a single dose of Melatonin comprising less than 1 mg to raise the peak plasma Melatonin levels to within physiological nocturnal levels of normal untreated individuals. In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Melatonin. A serving of the supplemental composition may include from about 0.001 g to about 0.01 g of Melatonin. The preferred dosage of a serving of the supplemental composition comprises about 0.0040 g of Melatonin. Furthermore, in an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include fine-milled Melatonin. A serving of the supplemental composition may include from about 0.0001 g to about 0.01 g of fine-milled Melatonin. The preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of fine-milled Melatonin. CoQ10
Coenzyme Q10 (CoQIO, ubiquinone) is found in the mitochondria of all cells and is involved in energy production. It is found at its highest concentrations in the heart, liver, kidney and pancreas. CoQIO is a potent antioxidant in human blood (Weber C, Sejersgard Jakobsen T, Mortensen SA, Paulsen G, Holmer G. Antioxidative effect of dietary coenzyme Q10 in human blood plasma., lnt J Vitam Nutr Res. 1994;64(4):311-5.) where it also acts to preserve vitamin E, another major antioxidant (Thomas SR, Neuzil J, Stacker R. Inhibition of LDL oxidation by ubiquinol-10. A protective mechanism for coenzyme Q in atherogenesis? MoI Aspects Med. 1997;18 Suppl:S85-103).
Due to its high concentrations in the heart, CoQ 10 is believed to benefit and strengthen the heart. Many heart-related diseases are thought to result from defective myocardial energy production and numerous studies have suggested that supplementation with CoQIO is beneficial (Mortensen SA. Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone). Clin Investig. 1993,71(8 Suppl):S116-23.). A meta-analysis of eight clinical trials supports the efficacy of CoQIO for the treatment of congestive heart failure (Soja AM, Mortensen SA. Treatment of congestive heart failure with coenzyme Q10 illuminated by meta-analyses of clinical trials. MoI Aspects Med. 1997;18 Suppl:S159-68.). Another study has shown that individuals suffering from angina were able to exercise for longer periods when receiving CoQIO (Kamikawa T, Kobayashi A, Yamashita T, Hayashi H, Yamazaki N. Effects of coenzyme Q10 on exercise tolerance in chronic stable angina pectoris. Am J Cardiol. 1985 Aug 1 ;56(4):247-51.) as compared to untreated groups. Moreover, myocardial function was improved by CoQIO in patients with disease conditions known to involve energy production deficits (Folkers K, Wolaniuk J, Simonsen R, Morishita M, Vadhanavikit S. Biochemical rationale and the cardiac response of patients with muscle disease to therapy with coenzyme Q10. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4513-6.) wherein these patients also reported a 'subjective' improved sense of well-being. CoQ.10 supplemented with iron and vitamin B6 has also appeared to prevent the progression of Alzheimer's disease, a neurological disease often associated with impaired mitochondrial function (Imagawa M, Naruse S, Tsuji S, Fujioka A, Yamaguchi H. Coenzyme Q10, iron, and vitamin B6 in genetically-confirmed Alzheimer's disease. Lancet. 1992 Sep 12;340(8820):671.). Moreover, in another neurological disorder, CoQIO in a phase Il clinical trial was reported to slow the progression of Parkinson's disease (Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M; Parkinson Study Group. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50.) which often results in disturbed sleep and has been shown to involve impaired mitochondrial function and low levels of CoQ10 (Shults CW, Haas RH, Passov D, Beal MF. Coenzyme Q10 levels correlate with the activities of complexes I and I I/I Il in mitochondria from parkinsonian and nonparkinsonian subjects. Ann Neurol. 1997 Aug;42(2):261-4.). Furthermore, CoQ10 has been successfully used to treat high blood pressure, eliminating the need for medication in many cases (Langsjoen P, Langsjoen P, Willis R, Folkers K. Treatment of essential hypertension with coenzyme Q10. MoI Aspects Med. 1994;15 Suppl:S265-72.). Migraines have also been successfully and safely treated with CoQIO (Sandor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005 Feb 22;64(4):713-5.) most likely due its effects on blood pressure.
In a Japanese study, CoQIO was shown to provide relieve from snoring in about half of the subjects, displaying a decrease in the sound level of their snoring (Takasaki Y, Yoshida H, Kaneko Y, Kaneda R, Kurosaki S, Yamadera Y., An Analysis of Effectiveness of Activated Co-enzyme Q10 on Subjects by Using Acoustic Technology. Biopharma Ltd. Tokyo Japan). Specifically, about 44% of subjects displayed a decrease in the sound level of their snoring during the REM stage of sleep, about 40% of subjects showed a decrease in the sound level of their snoring during non-REM sleep stages l/ll, and about 33% of subjects showed a decrease in the sound level of their snoring during non-REM sleep stages III/IV. Furthermore, subjects reported in questionnaires that their feeling of restfulness was improved upon waking.
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include CoEnzyme Q10. A serving of the supplemental composition may include from about 0.0005 g to about 0.1000 g of CoEnzyme Q10. The preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of CoEnzyme Q 10. Lemon Balm Leaf Extract The plant Melissa officinalis, commonly known as Lemon balm is a member of the mint family and is often referred to as 'the calming herb". Lemon balm extract has proven antioxidant activity which likely contributes to its beneficial effects (Hohmann J, Zupko I, Redei D, Csanyi M, Falkay G, Mathe I, Janicsak G. Protective effects of the aerial parts of Salvia officinalis, Melissa Officinalis and Lavandula angustifolia and their constituents against enzyme- dependent and enzyme-independent lipid peroxidation. Planta Med. 1999 Aug;65(6):576-8.). However, in the central nervous system, it possesses acetylcholine receptor activity (Wake G, Court J, Pickering A, Lewis R, Wilkins R, Perry E. acetylcholine receptor activity in European medicinal plants traditionally used to improve failing memory. J Ethnopharmacol. 2000 Feb;69(2):105-14.), therefore suggesting that it may have another possible mechanism of action relating to cell-signaling.
Randomized, placebo-controlled, double-blind clinical studies investigating the acute effects of Lemon balm extract on cognition and mood have demonstrated a calming effect (Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav. 2002 Jul;72(4):953-64.) in addition to the effect of improved mood (Kennedy DO, Wake G, Savelev S, Tildesley NT, Perry EK, Wesnes KA, Scholey AB. Modulation of mood and cognitive performance following acute administration of single doses of Melissa officinalis (Lemon balm) with human CNS nicotinic and muscarinic receptor-binding properties. Neuropsychopharmacology. 2003 Oct;28(10):1871-81.)- Lemon balm extract has also shown potential in reducing the negative mood effects of stress in clinical trials (Kennedy DO, Little W, Scholey AB. Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosom Med. 2004 JuI- Aug;66(4):607-13.).
Moreover, the cognitive function of Alzheimer's patients has been shown to be improved by the use Lemon balm extract (Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi AH, Khani M. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):863-6.). In this study, the treatment group also displayed less agitation than the placebo group, suggesting an improvement in mood. Furthermore, clinical trials have demonstrated that Lemon balm can be effective at reducing stress and anxiety when used in combination with Valeriana (Kennedy DO, Little W, Haskell CF, Scholey AB. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress. Phytother Res. 2006 Feb;20(2):96-102.). Another study has shown that when presented in a lozenge also containing Lavender oil and hops, Lemon balm can alter brainwaves related to working memory, leading to the induction of a state of relaxation and an improved ability to cope with emotional and physiological stress (Dimpfel W, Pischel I, Lehnfeld R. Effects of lozenge containing lavender oil, extracts from hops, lemon balm and oat on electrical brain activity of volunteers. Eur J Med Res. 2004 Sep 29;9(9):423-31.). In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Lemon Balm leaf extract. A serving of the supplemental composition may include from about 0.0010 g to about 0.1000 g of Lemon Balm leaf extract. The preferred dosage of a serving of the supplemental composition comprises about 0.0800 g of Lemon Balm leaf extract. Hops cone extract (Humulus lupulus)
The hop plant (Humulus lupulus) is a flowering vine used traditionally as a sedative to assist with anxiety reduction and sleep difficulties. In mice, hops extract displays sleep-enhancing and antidepressant activities (Zanoli P, Rivasi
M, Zavatti M, Brusiani F, Baraldi M. New insight in the neuropharmacology activity of Humulus lupulus L. J Ethnopharmacol. 2005 Oct 31 ;102(1):102-6.).
In vitro tests have shown that hops contain compounds with antioxidant and chemoprotective activity as well as compounds that can induce detoxification enzymes (Dietz BM, Kang YH, Liu G, Eggler AL, Yao P, Chadwick LR, Pauli GF, Farnsworth NR, Mesecar AD, van Breemen RB, Bolton JL. Xanthohumol isolated from Humulus lupulus Inhibits menadione-induced DNA damage through induction of quinone reductase. Chem Res Toxicol. 2005 Aug;18(8):1296-305.).
A combination of valerian and hops has been shown to interact with adenosine receptors (Muller CE, Schumacher B, Brattstrom A, Abourashed EA,
Koetter U. Interactions of valerian extracts and a fixed valerian-hop extract combination with adenosine receptors. Life Sci. 2002 Sep 6;71(16):1939-49.) to aid in the maintenance of sleep. Moreover, binding of the valerian-hop combination to melatonin and serotonin receptors has also been shown (Abourashed EA, Koetter U, Brattstrom A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004 Nov;11(7-8):633-8.). These two receptor types are also known to be involved in the sleep process. Furthermore, hop extract has been shown to modulate the gamma-aminobutyric acid receptor (GABA(A) receptors) and display GABA-like activity (Aoshima H, Takeda K, Okita Y, Hossain SJ, Koda H, Kiso Y. Effects of beer and hop on ionotropic gamma-aminobutyric acid receptors. J Agric Food Chem. 2006 Apr 5;54(7):2514- 9.) relating to sleep. GABA is an inhibitory neurotransmitter that can induce relaxation and sleep. Modulation of any or all of these receptors may mediate the sleep-inducing activity of hops.
Most of the studies examining the efficacy of hops to aid sleep employ hops in combination with other compounds acting on various receptors known to be involved in sleep regulation. A combination of valerian and hops has been shown to reduce the time taken to fall asleep and results in a more refreshed feeling in the morning in subjects suffering from mild to moderate insomnia (Fussel A, Wolf A, Brattstrom A. Effect of a fixed valerian-Hop extract combination (Ze 91019) on sleep polygraphy in patients with non-organic insomnia: a pilot study. Eur J Med Res. 2000 Sep 18;5(9):385-90.).
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Hops cone extract. A serving of the supplemental composition may include from about 0.0010 g to about 0.1000 g of Hops cone extract. The preferred dosage of a serving of the supplemental composition comprises about 0.0200 g of Hops cone extract.
Lavender Flower (Lavandula officinalis) Oil from Lavandula officinalis, commonly known as the Lavender plant is frequently used in aromatherapy as a mode to induce relaxation. The mild sedative effects of Lavender have been demonstrated in animals and humans (Lis-Balchin M, Hart S. Studies on the mode of action of the essential oil of lavender (Lavandula angustifolia P. Miller). Phytother Res. 1999 Sep;13(6):540- 2.). Further to the sedative effect, Lavender oil has been shown to reduce agitation of patients suffering from dementia (Holmes C, Hopkins V, Hensford C, MacLaughlin V, Wilkinson D, Rosenvinge H. Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study, lnt J Geriatr Psychiatry. 2002 Apr;17(4):305-8.). Moreover, Lavender has also been shown be beneficial for treating depression (Akhondzadeh S, Kashani L, Fotouhi A, Jarvandi S, Mobaseri M, Moin M, Khani M, Jamshidi AH, Baghalian K, Taghizadeh M. Comparison of Lavandula angustifolia Mill, tincture and imipramine in the treatment of mild to moderate depression: a double-blind, randomized trial. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Feb;27(1 ):123-7.). Additionally, the sleep-inducing effects of other compounds may be increased by Lavender (Gyllenhaal C, Merritt SL, Peterson SD, Block Kl, Gochenour T. Efficacy and safety of herbal stimulants and sedatives in sleep disorders. Sleep Med Rev. 2000 Jun;4(3):229-251.). U.S. Patent No. 5,958,462, entitled "Therapeutic Bath Salts and Method of Use," describes a composition comprising magnesium, carbonate and copper compounds and optionally essential oils including that of Lavender. The composition comprises bath salts purported to be helpful in the relaxation of muscles, elimination or reduction of muscle spasms, and the overall enhancement of a person's mood when used as an aromatherapy.
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Lavender Flower powder. A serving of the supplemental composition may include from about 0.0010 g to about 0.0100 g of Lavender Flower powder. The preferred dosage of a serving of the supplemental composition comprises about 0.0050 g of Lavender Flower powder. Passion Flower Extract
Passion flower has been used traditionally for relaxation and as a sleep- aid as well as a treatment for anxiety. The main active component of Passionflower is thought to by chrysin, one of several flavonoids which have been isolated from this plant (Menghini A, Mancini LA. TLC determination of flavonoid accumulation in clonal populations of Passiflora incarnata L. Pharmacol Res Commun. 1988 Dec;20 Suppl 5:113-6.; Pereira CA, Yariwake JH, Lancas FM, Wauters JN, Tits M, Angenot L. A HPTLC densitometric determination of flavonoids from Passiflora alata, P. edulis, P. incarnata and P. caerulea and comparison with HPLC method. Phytochem Anal. 2004 Jul-Aug;15(4):241-8.). In mice, chrysin has been shown to act as an agonist of benzodiazepine receptors and also possess anti-anxiety activity (Wolfman C, Viola H, Paladini A, Dajas F, Medina JH. Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol Biochem Behav. 1994 Jan;47(1 ):1-4.). Studies have shown that, in mice, Passionflower extract reduces anxiety and induces sleep (Soulimani R, Younos C, Jarmouni S, Bousta D, Misslin R, Mortier F. Behavioural effects of Passiflora incamata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol. 1997 Jun;57(1):11-20.). Clinical trials in humans have further demonstrated that Passionflower is effective in the treatment of anxiety (Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 2001 Oct;26(5):363-7.).
One aspect of the present invention includes the use of Passionflower extract for the reduction of stress and anxiety. U.S. Patent Nos. 6,080,410 and 5,681 ,578 describe a method and composition, respectively, employing Passionflower extracts for the reduction of stress and anxiety.
U.S. Patent No. 6,080,410, entitled "Method for Reducing Daily Stress and Anxiety in Adults," describes a method of employing a novel dietary supplement which serves a general relaxant comprised of Kava root extract, and at least one of Passionflower, Chamomile Flower, Hops, and Schizandra Fruit. The method claims to reduce daily stress and anxiety in adults. It is administered in capsule format. U.S. Patent No. 5,681 ,578, entitled "Composition for Relieving Stress
Anxiety, Grief, And Depression," describes a composition comprising gamma
Aminobutyric acid, glutamine, glycine, magnesium, passionflower, primal officinalis and vitamin B6. The composition is purported to relieve stress, anxiety, grief and depression.
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Passionflower extract. A serving of the supplemental composition may include from about 0.0010 g to about 0.0100 g of Passionflower extract. The preferred dosage of a serving of the supplemental composition comprises about 0.0020 g of Passionflower extract. Skullcap {Scutellaria lateriflora)
Scutellaria, also known commonly as Skullcap, is a member of the mint family and has been used traditionally to treat depression and stress. Studies in mice indicate that Skullcap reduces anxiety (Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003 Nov;10(8):640-9.). The effects of Skullcap may be at least partially mediated by antagonism of serotonin receptors (Gafner S, Bergeron C, Batcha LL, Reich J, Arnason JT, Burdette JE, Pezzuto JM, Angerhofer CK. Inhibition of [3H]-LSD binding to 5-HT7 receptors by flavonoids from Scutellaria lateriflora. J Nat Prod. 2003 Apr;66(4):535-7.). A clinical study involving healthy volunteers also demonstrated that Skullcap reduces anxiety (Wolfson P, Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. Altern Ther Health Med. 2003 Mar-Apr;9(2):74- 8.).
U.S. Patent No. 7,045,158, entitled "Standardized Extracts of Scutellaria Laterifloa," describes an improved extract of Scutellaria Laterifloa and relates to a pharmaceutical composition prepared from said extract wherein it is suitable for treating anxiety, insomnia, convulsions, muscle tension and spasms.
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Skullcap powder. A serving of the supplemental composition may include from about 0.0001 g to about 0.0100 g of Skullcap powder. The preferred dosage of a serving of the supplemental composition comprises about 0.0010 g of Skullcap powder. Valerian Root (Valeriana officinalis) Valeriana officinalis, wherein the root, normally called Valerian root, is a perennial herb traditionally used as a sedative and sleep-aid. Compounds from Valerian interact with GABA, melatonin, and/or adenosine systems through binding to certain melatonin and serotonin receptor subtypes (Abourashed EA, Koetter U, Brattstrom A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004 Nov;11(7-8):633-8.), particularly the 5-HT5A subtype (Dietz BM, Mahady GB, Pauli GF, Famsworth NR. Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res MoI Brain Res. 2005 Aug 18;138(2):191-7.). Interaction with this receptor is thought to be responsible for the sleep-inducing and maintenance effect of Valerian root extract.
Valerian root extract has proven to be useful in several clinical trials. Subjective self-evaluation of sleep quality improved in a valerian supplemented group as part of a randomized controlled trial (Leathwood PD, Chauffard F1 Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav. 1982 JuI; 17(1 ):65- 71.), compared to control groups. In another clinical trial, the valerian group reported improved sleep over the placebo group, with 89% of participants reporting improved sleep (Lindahl O, Lindwall L. Double blind study of a valerian preparation. Pharmacol Biochem Behav. 1989 Apr;32(4): 1065-6.). Sleep was additionally improved in children with various intellectual deficits, particularly those with hyperactivity (Francis AJ, Dempster RJ. Effect of valerian, Valeriana edulis, on sleep difficulties in children with intellectual deficits: randomised trial. Phytomedicine. 2002 May;9(4):273-9.).
One aspect of the present invention includes the use of Valerian for improving the quality of sleep and reducing minor aches and pains. U.S. Patent Nos. 6,869,622 and 6,383,527 describe respective compositions for improving the quality of sleep and alleviating muscular aches and strains, particularly with respect to those in the lower back.
For example, U.S. Patent No. 6,869,622, entitled "Composition for Improving Sleep Quality and Efficiency, And Method of Preparing and Using the Composition," describes a pharmaceutically active extract of the plant root family of Valerianaceae and its usefulness in improving sleep quality and efficiency. The patent purports to relate to a method for reducing the number of times a patient wakes after sleep onset, comprising administering to the patient a pharmaceutically-active extract of the root of a plant of the family Valerianaceae, wherein it is processed via an ethanolic and water extraction. Furthermore, a single dosage is administered between the range of 50 mg and 5000 mg approximately one-half and two hours prior to bedtime.
U.S. Patent No. 6,383,527, entitled "Compositions Comprising Valerian Extracts, Isovaleric Acid or Derivatives Thereof with a NSAID," purports to describe a combination of valerian extract or isovaleric acid or a derivative in with a non-steroidal anti-inflammatory compound for treating acute muscular aches, strains and sprains, and in particular lower back pain.
In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Valerian Root. A serving of the supplemental composition may include from about 0.1000 g to about 1.000 g of Valerian Root. The preferred dosage of a serving of the supplemental composition comprises about 0.1200 g of Valerian Root. Willow bark extract (providing salicin) (Salix alba) 25% salicin Willow bark (Salix alba) is a source of salicin, a precursor of acetylsalicylic acid (aspirin) traditionally used to treat pain, fever and inflammation. In a blind clinical trial, willow bark was demonstrated to be effective at relieving back pain (Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, Conradt C. Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Am J Med. 2000 Jul;109(1 ):9-14.). After four weeks, 39% of the high salicin group (n=65) were pain-free, 21% of the low salicin group (n=67) were pain-free, and only 6% of the placebo group (n=59) were pain-free. Willow bark extract has also been shown to effectively reduce arthritis pain (Schmid B, Ludtke R, Selbmann HK, Kotter I, Tschirdewahn B, Schaffner W, Heide L. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: randomized placebo-controlled, double blind clinical trial. Phytother Res. 2001 Jun;15(4):344-50.). The diminishment of bodily pain is an integral part of quality sleep. The inclusion of Willow Back Extract aids in the alleviation of minor bodily pains, leading to an improvement in sleep quality and a reduction in sleep disruption due to discomfort.
One aspect of the present invention includes the use of Willow bark for the attenuation of minor aches and pains, leading to an improved quality of sleep. U.S. Patent Nos. 6,770,263 and 6,312,736 describe compositions for the treatment, e.g., alleviation, of aches and pains.
For example, U.S. Patent No. 6,770,263, entitled "Compositions and Methods for the Treatment of Aches and Pains," purports to describe methods and compositions useful for treating aches and/or pains. The composition comprises an aqueous medium having dispersed or dissolved therein an analgesic selected from the group consisting of white willow bark, aspirin, ibuprofen, naproxen, and any combination thereof. The composition is then administered in an effective amount across a mucosal membrane.
U.S. Patent No. 6,312,736, entitled "Herbal Composition to Relieve Pain," describes a composition used to relieve pain and other symptoms associated with migraines and other types of headaches. The composition comprises a combination of White Willow bark extract, Kava Kava root extract, Feverfew extract, Ginger root extract, Guarana extract, and Vitamin B6 wherein the composition may be combined with liposomes to carry the composition in a sublingual dosage for fast pain relief. In an embodiment of the present invention, which is set forth in greater detail in Example 1 below, the supplemental composition may include Willow bark extract. A serving of the supplemental composition may include from about 0.1000 g to about 1.000 g of Willow bark extract. The preferred dosage of a serving of the supplemental composition comprises about 0.1500 g Willow bark extract.
The present invention, according to an embodiment thereof, provides a method which includes the step of consuming a composition, wherein the method may, for example, alleviate minor aches and pains, speedily induce sleep, as well as provide for maintenance of sleep thereby promoting a good quality, restful sleep. In an embodiment of the present invention, the method includes the daily consumption, prior to going to sleep with the intent of a full night's sleep, of a sleep-promoting and pain-relief composition that may include at least an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof. Furthermore, the sleep-promoting and pain-relief composition may further comprise Coenzyme Q 10, Lemon Balm leaf extract, Hops cone extract, Lavender flower extract, Passionflower extract, and Skullcap powder.
The present supplemental composition, or those similarly envisioned by one of skill in the art, may be utilized in methods to alleviate minor aches and pains, speedily induce sleep, as well as provide for maintenance of sleep thereby promoting a good quality, restful sleep in a formulation designed to be consumed on a daily basis prior to going to sleep with the intent of a night's rest.
In an embodiment of the present invention, the composition may include a time-release mechanism, e.g., wherein the time-release mechanism provides 4 hours of active compound release. Also, in various embodiments, the melatonin may be incorporated into a tablet coating to promote sleep more quickly, e.g., to promote instant or immediate sleep.
Although the following example illustrates the practice of the present invention one of its embodiments the example should not be interpreted as limiting the scope of the invention. Other embodiments of the present invention will be apparent to those of skill in the art form consideration of the specification and example.
Example 1
A supplemental composition is provided on a daily basis, prior to going to sleep with the intent on a full night's rest, the composition utilizing a dual-release caplet formulation comprising Melatonin (0.0040 g), fine-milled Melatonin (0.0010 g), Coenzyme Q10 (0.0010 g), Hops cone extract (0.0200 g), Lavender flower powder (0.0050 g), Passionflower extract (0.0020 g), Skullcap powder (0.0010 g), Lemon Balm leaf extract (0.0800 g), deodorized Valerian root (0.1200 g) and Willow bark extract (0.1500 g).
Directions: As a supplemental composition, 1 caplet is orally administered with an 8 oz. glass of water once daily prior to going to sleep. Preferably, the supplemental composition is consumed with the intent of a full night's sleep.

Claims

ClaimsWhat is claimed:
1. A composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
2. The composition of claim 1 , further comprising an extract of Hops cone.
3. The composition of claim 2, further comprising Lavender flower powder.
4. The composition of claim 3, further comprising an extract of Passionflower.
5. The composition of claim 4, further comprising Skullcap powder.
6. The composition of claim 5, further comprising an extract of Coenzyme Q10.
7. The composition of claim 6, further comprising a leaf of extract Lemon Balm.
8. The composition of claim 7, further comprising a time-release mechanism.
9. The composition of claim 8, wherein at least a portion of the melatonin is fine-milled.
10. The composition of claim 1 , wherein the extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof, are provided in amounts effective to at least one of promote sleep and relieve pain.
11. The composition of claim 1 , wherein the composition is provided in a tablet form.
12. The composition of claim 11 , wherein the melatonin or derivative thereof is incorporated into a coating of the tablet, so as to promote sleep more quickly.
13. A composition comprising: about 0.1200 g of an extract of Valerian Root per serving; about 0.1500 g of an extract of Willow Bark per serving; about 0.0040 g of Melatonin per serving; about 0.0010 g of fine-milled Melatonin per serving; about 0.020Og of an extract of Hops cone per serving; about 0.0050 g of Lavender flower powder per serving; about 0.0020 g of an extract of Passionflower per serving; about 0.0010 g of Skullcap powder per serving; about 0.0010 g of Coenzyme Q10 per serving; and about 0.0800 g of an extract of Lemon Balm per serving.
14. A method for at least one of promoting sleep and relieving pain, the method comprising the step of: administering to a human or animal a composition comprising an extract of Valerian Root, an extract of Willow Bark and Melatonin or a derivative thereof.
15. The method of claim 14, wherein promoting sleep includes at least one of inducing sleep and maintaining sleep.
16. The method of claim 14, wherein the composition is administered to a user once daily prior to the user going to sleep.
17. The method of claim 16, wherein the composition is provided with a time- release mechanism.
18. The method of claim 17, wherein the time-release mechanism provides about 4 hours of active compound release.
19. The method of claim 18, wherein composition is provided in the form of a tablet, and the melatonin or derivative thereof is incorporated into a coating of the tablet to promote sleep more quickly.
20. The method of claim 14, wherein the composition further comprises an extract of Hops cone.
21. The method of claim 20, wherein the composition further comprises
Lavender flower powder.
22. The method of claim 21 , wherein the composition further comprises an extract of Passionflower.
23. The method of claim 22, wherein the composition further comprises Skullcap powder.
24. The method of claim 23, wherein the composition further comprises an extract of Coenzyme Q10.
25. The method of claim 24, wherein the composition further comprises a leaf of extract Lemon Balm.
26. The method of claim 25, wherein the composition further comprises a time-release mechanism.
27. The method of claim 26, wherein at least a portion of the melatonin is fine- milled.
PCT/CA2006/001156 2006-02-23 2006-07-14 Compositions and methods for the induction and maintenance of quality sleep WO2007095716A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002642761A CA2642761A1 (en) 2006-02-23 2006-07-14 Compositions and methods for the induction and maintenance of quality sleep
JP2008555578A JP2009527504A (en) 2006-02-23 2006-07-14 Compositions and methods for induction and maintenance of good quality sleep
EP06761118A EP1991241A4 (en) 2006-02-23 2006-07-14 Compositions and methods for the induction and maintenance of quality sleep
AU2006338839A AU2006338839A1 (en) 2006-02-23 2006-07-14 Compositions and methods for the induction and maintenance of quality sleep

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77632506P 2006-02-23 2006-02-23
US60/776,325 2006-02-23

Publications (1)

Publication Number Publication Date
WO2007095716A1 true WO2007095716A1 (en) 2007-08-30

Family

ID=38433828

Family Applications (5)

Application Number Title Priority Date Filing Date
PCT/CA2006/001156 WO2007095716A1 (en) 2006-02-23 2006-07-14 Compositions and methods for the induction and maintenance of quality sleep
PCT/CA2006/001345 WO2007095717A1 (en) 2006-02-23 2006-08-16 Rapidly dissolving solid oral dosage form for delivery of composition for increasing nitric oxide activity
PCT/CA2006/001512 WO2007095718A1 (en) 2006-02-23 2006-09-14 Nutritional composition and method for increasing creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and for aiding recovery following exercise
PCT/CA2007/000263 WO2007095734A1 (en) 2006-02-23 2007-02-21 Method for increasing the rate and consistency of bioavailability of supplemental dietary ingredients
PCT/CA2007/000262 WO2007095733A1 (en) 2006-02-23 2007-02-21 Method for a supplemental dietary composition having a multi-phase dissolution profile

Family Applications After (4)

Application Number Title Priority Date Filing Date
PCT/CA2006/001345 WO2007095717A1 (en) 2006-02-23 2006-08-16 Rapidly dissolving solid oral dosage form for delivery of composition for increasing nitric oxide activity
PCT/CA2006/001512 WO2007095718A1 (en) 2006-02-23 2006-09-14 Nutritional composition and method for increasing creatine uptake and retention in skeletal muscle, increasing muscle mass and strength, increasing exercise capacity and for aiding recovery following exercise
PCT/CA2007/000263 WO2007095734A1 (en) 2006-02-23 2007-02-21 Method for increasing the rate and consistency of bioavailability of supplemental dietary ingredients
PCT/CA2007/000262 WO2007095733A1 (en) 2006-02-23 2007-02-21 Method for a supplemental dietary composition having a multi-phase dissolution profile

Country Status (7)

Country Link
US (8) US7476405B2 (en)
EP (2) EP1991241A4 (en)
JP (1) JP2009527504A (en)
AU (2) AU2006338839A1 (en)
CA (3) CA2642761A1 (en)
WO (5) WO2007095716A1 (en)
ZA (1) ZA200807489B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010215561A (en) * 2009-03-17 2010-09-30 Shiseido Co Ltd Circadian rhythm-adjusting agent
WO2012112116A1 (en) * 2011-02-16 2012-08-23 Wellbemed Sweden Ab Foodstuff comprising an extract mixture
CN103476274A (en) * 2011-04-18 2013-12-25 雀巢产品技术援助有限公司 Nutritional compositions having alpha-hica and alpha-ketoglutarate

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1973406T3 (en) 2005-12-28 2014-06-23 Advanced Bionutrition Corp Feed agent for probiotic bakeries comprising a dry blend of polysaccharides, saccharides, glassy polyols
US20080254121A1 (en) * 2007-04-10 2008-10-16 Iomedix Sleep International Srl Multi-layer melatonin composition
JP5714227B2 (en) * 2007-05-31 2015-05-07 サントリーホールディングス株式会社 Anti-fatigue agent and oral composition containing andrographolide as active ingredient
IE86322B1 (en) * 2007-10-10 2013-12-18 Daniel Farrington A homeopathic complex
US20090156634A1 (en) * 2007-12-12 2009-06-18 Iovate T. & P. Inc. Tropane alkaloids and trigonelline combinations and methods for administering the same
US20090203789A1 (en) * 2008-01-31 2009-08-13 Multi Formulations Ltd. Fast Dissolution Amino Acid Composition
US20090304602A1 (en) * 2008-06-06 2009-12-10 Tuchinsky David B Nutritional supplement
US20110123654A1 (en) * 2008-06-06 2011-05-26 Ralf Jaeger Synergistic enhancement of cellular ergogenic nutrient uptake, like creatine or carnitine, with tarragon
WO2010019266A2 (en) * 2008-08-15 2010-02-18 Ironwood Pharmaceuticals, Inc. Stable solid formulation of a gc-c receptor agonist polypeptide suitable for oral administration
US20100124587A1 (en) * 2008-11-17 2010-05-20 Heuer Marvin A Creatine-containing vitamin and mineral composition
US20100256215A1 (en) * 2009-04-02 2010-10-07 Silver Eagle Labs Nv, Llc Menthol-Melatonin Dissolving Film
US20100256197A1 (en) * 2009-04-02 2010-10-07 Silver Eagle Labs Nv, Llc Nicotine Dissolving Film With Or Without Menthol
RU2567668C2 (en) 2009-05-26 2015-11-10 Эдванст Бионутришн Корпорейшн Stable dry powder composition containing biologically active microorganisms and/or biologically active materials and method of its production
MX2012001660A (en) * 2009-08-06 2012-03-26 Ironwood Pharmaceuticals Inc Linaclotide-containing formulations for oral administration.
US9445622B2 (en) * 2009-12-21 2016-09-20 Glanbia Nutritionals (Ireland) Ltd. Compositions and methods for improving creatine solubility and stability
WO2011084816A1 (en) * 2009-12-21 2011-07-14 Glanbia Nutritionals (Ireland) Ltd. Leucine/peptide composition and method of formulation
US9504750B2 (en) 2010-01-28 2016-11-29 Advanced Bionutrition Corporation Stabilizing composition for biological materials
BR112012018839B1 (en) 2010-01-28 2020-04-14 Advanced Bionutrition Corp dry glassy composition comprising a bioactive material
WO2011098394A2 (en) 2010-02-09 2011-08-18 Reiner Rittinghausen Composition for the treatment and prevention of anxiety disorders and dyssomnia
UA108636C2 (en) 2010-02-17 2015-05-25 PEPTIDE
US8828453B2 (en) * 2010-04-29 2014-09-09 Betul Hatipoglu Herbal-based compositions for alleviating symptoms associated with autism
US20120003304A1 (en) * 2010-07-02 2012-01-05 Fmc Corporation Solid Forms
JP5921545B2 (en) 2010-08-11 2016-05-24 アイアンウッド ファーマシューティカルズ インコーポレイテッド Stable formulation of linaclotide
US10869843B2 (en) 2010-11-23 2020-12-22 Chemi Nutra Method for increasing muscle mass and strength
US9532952B2 (en) 2011-01-28 2017-01-03 Physician's Seal, LLC Controlled-release compositions of melatonin combined with sedative and/or analgesic ingredients
US8691275B2 (en) 2011-01-28 2014-04-08 Zx Pharma, Llc Controlled-release melatonin compositions and related methods
UA113291C2 (en) 2011-08-04 2017-01-10 TRANSCLOMYPHENE METABOLITES AND THEIR APPLICATIONS
CA2846230A1 (en) 2011-08-17 2013-02-21 Ironwood Pharmaceuticals, Inc. Treatments for gastrointestinal disorders
ITUD20110196A1 (en) 2011-12-02 2013-06-03 Asoltech S R L COMPOSITION BASED ON UBIDECARENONE
US20150202167A1 (en) * 2012-08-21 2015-07-23 Repros Therapeutics Inc. Trans-Clomiphene Formulations and Uses Thereof
JP2015535283A (en) 2012-11-02 2015-12-10 レプロス セラピューティクス インコーポレイティド Trans-clomiphene for use in cancer therapy
WO2015050809A1 (en) * 2013-10-01 2015-04-09 Novozymes A/S Processes of producing fermentation products
ES2633360T3 (en) * 2014-04-02 2017-09-20 Alzchem Ag Creatine and protein matrix as well as procedure for the production of this matrix
AU2015257871B2 (en) * 2014-05-05 2019-09-12 A. Nattermann & Cie. Gesellschaft mit Beshränkter Haftung Fast dissolving granulate
PL2974733T3 (en) * 2014-07-14 2017-09-29 Dr. Willmar Schwabe Gmbh & Co. Kg Combination of valerian root extract and lavender oil for use in the treatment of sleep disorders
ES2949137T3 (en) 2014-11-14 2023-09-25 Asoltech Srl Composition based on coq10 field of invention
MY194231A (en) 2015-07-29 2022-11-23 Advanced Bionutrition Corp Stable dry probiotic compositions for special dietary uses
US10674746B2 (en) 2015-10-27 2020-06-09 Cytozyme Animal Nutrition, Inc. Animal nutrition compositions and related methods
CN108473384A (en) 2015-10-27 2018-08-31 细胞酶动物营养品公司 Animal nutrition ingredient and correlation technique
CN106674057A (en) * 2015-11-09 2017-05-17 江西乐维生物药业有限公司 L-arginine alpha-ketoisocaproate preparation method
WO2017109300A1 (en) * 2015-12-22 2017-06-29 Urgo Recherche Innovation Et Developpement Combination product that helps relax and fall asleep
CN109310638A (en) * 2016-05-06 2019-02-05 医师印章有限责任公司 Valerian composition and correlation technique
JP7007798B2 (en) * 2016-09-13 2022-02-10 オリザ油化株式会社 Circadian rhythm improver
JP6909569B2 (en) * 2016-09-16 2021-07-28 オリザ油化株式会社 Skin quality improver
ES2684414B1 (en) * 2017-03-31 2019-12-11 Laboratorios Vinas S A Galenic composition, for oral use, comprising micronized melatonin and a zinc salt and corresponding method and use
BR122021012549B8 (en) 2017-06-20 2022-10-25 Physicians Seal Llc ORAL MELATONIN DISSOLUTION COMPOSITION WITH ACIDIFYING AGENT THAT MAKES MELATONIN SOLUBLE IN SALIVA
WO2019005962A1 (en) * 2017-06-27 2019-01-03 Harmonix, Llc Time release sleep aid system
EP3678648B1 (en) 2017-09-08 2023-07-26 Insignis Therapeutics, Inc. Methods of using dipivefrin
US10639340B2 (en) * 2018-06-18 2020-05-05 Eric Young Method of drying botanicals
KR102154074B1 (en) 2018-10-17 2020-09-09 한국 한의학 연구원 Composition for preventing, ameliorating or treating sleep disturbance comprising flavonoid compound as effective component
CN110876691A (en) * 2019-10-29 2020-03-13 广东润和生物科技有限公司 Coenzyme Q10Sleep-aiding skin-beautifying massage emulsion
WO2021086271A1 (en) 2019-10-31 2021-05-06 Mark One Innovation Center Company Limited A composition containing mulberry extract and production method thereof
US20210299166A1 (en) * 2020-03-25 2021-09-30 Allgood Beverage Company Compositions for maintaining electrolyte balance and urinary tract health
US20240000780A1 (en) * 2020-12-01 2024-01-04 Seattle Gummy Company Ped5 inhibitor semi-solid compositions and methods of making and using thereof
US20220347119A1 (en) * 2021-04-30 2022-11-03 Reshma N. Kheraj Medicated drink
US11833182B2 (en) 2021-08-10 2023-12-05 Shaklee Corporation Sleep product
CN114027508A (en) * 2021-12-03 2022-02-11 龙岩学院 Functional food gamma-aminobutyric acid compound preparation for improving sleep
EP4444291A1 (en) * 2021-12-08 2024-10-16 Nutramax Laboratories, Inc. Supplemental coating and related method
GB2627641A (en) * 2021-12-08 2024-08-28 Nutramax Lab Inc Supplemental coating and related method
DE102022114966A1 (en) 2022-06-14 2023-12-14 Alzchem Trostberg Gmbh Water-soluble creatine agglomerate
CN115381890A (en) * 2022-08-01 2022-11-25 澳美制药(苏州)有限公司 Sleep-aiding sustained-release tablet and preparation method thereof
WO2024186797A1 (en) * 2023-03-07 2024-09-12 Gtf, Llc Method of processing hops plants into pellets, feedstock, and fertilizer

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6770263B1 (en) * 2001-10-01 2004-08-03 Naturewell, Incorporated Compositions and methods for the treatment of aches and pains
US20040234544A1 (en) * 2001-08-09 2004-11-25 Ralf Jager Formulation containing (lyso-)phosphatidylserine for the prevention and treatment of stress states in warm blooded animals
US6869622B2 (en) * 1999-07-21 2005-03-22 Ancile Pharmaceuticals, Inc. Composition for improving sleep quality and efficiency, and methods of preparing and using the composition
US20050129783A1 (en) * 2001-04-19 2005-06-16 Mccleary Edward L. Composition and method for treatment of neurophysiological conditions and maintenance of neurophysiological health

Family Cites Families (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4006025A (en) * 1975-06-06 1977-02-01 Polaroid Corporation Process for dispersing sensitizing dyes
US4294916A (en) * 1979-05-22 1981-10-13 Ciba-Geigy Ag Photographic silver halide material containing a dye filter or a dye anti-halation layer
US4294917A (en) * 1979-05-22 1981-10-13 Ciba-Geigy Ag Photographic silver halide material containing a dye filter or a dye anti-halation layer
GB2057420B (en) * 1979-08-30 1984-05-10 Standard Telephones Cables Ltd Controlled release glass
US4490654A (en) * 1983-06-10 1984-12-25 The Arthur G. Russell Company, Incorporated Control circuit for vibratory devices
US4781925A (en) 1986-03-06 1988-11-01 American Home Products Corporation Calcium supplement compressed tablets
US5520932A (en) * 1988-06-24 1996-05-28 The Upjohn Company Fine-milled colestipol hydrochloride
US4927744A (en) * 1988-08-05 1990-05-22 Eastman Kodak Company Photographic element having solid particle dispersion oxidized developer scavenger
US4950586A (en) * 1988-12-23 1990-08-21 Eastman Kodak Company Solid particle dispersions of filter dyes for photographic elements
US5242941A (en) 1990-12-04 1993-09-07 State Of Oregon Methods of treating circadian rhythm disorders
US5145684A (en) * 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
HUT62477A (en) * 1991-10-07 1993-05-28 Sandor Milesz Herb mixture
GB9215746D0 (en) * 1992-07-24 1992-09-09 Hultman Eric A method of increasing creatine supply depot
US5449683A (en) 1992-10-01 1995-09-12 Massachussetts Institute Of Technology Methods of inducing sleep using melatonin
US5547683A (en) * 1992-10-09 1996-08-20 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Method for producing microgranulated particle
EP0729357B1 (en) * 1993-11-19 2005-02-02 Janssen Pharmaceutica N.V. Microencapsulated 1,2-benzazoles
IT1271687B (en) * 1994-08-04 1997-06-04 Flamma Spa WATER SOLUBLE ORGANIC SALTS OF CREATINE
JPH07252148A (en) * 1994-10-08 1995-10-03 Masahiro Nagahama Therapeutic agent for diabetes
US5726146A (en) * 1994-12-06 1998-03-10 Natural Supplement Association, Incorporated Non-steroidal, anabolic dietary supplement and method to increase lean mass without linked increase fat mass
GB9517443D0 (en) * 1994-12-17 1995-10-25 Univ Nottingham Increasing creatine and glycogen concentration in muscle
US5541801A (en) * 1995-05-26 1996-07-30 United Microelectronics Corporation Low-voltage gate trigger SCR (LVGTSCR) ESD protection circuit for input and output pads
US5681578A (en) 1996-01-22 1997-10-28 Sahley; Billie J. Composition for relieving stress anxiety, grief, and depression
DK0904060T3 (en) 1996-05-20 2004-04-13 Janssen Pharmaceutica Nv Antifungal preparations with improved bioavailability
GB9611356D0 (en) * 1996-05-31 1996-08-07 Howard Alan N Improvements in or relating to compositions containing Creatine, and other ergogenic compounds
US8128955B2 (en) * 1996-05-31 2012-03-06 The Original Creatine Patent Company Food compositions containing creatine
US6361794B1 (en) * 1996-06-12 2002-03-26 Basf Corporation Method of making ibuprofen and narcotic analgesic composition
US6080410A (en) 1997-03-17 2000-06-27 Natrol, Inc. Method for reducing daily stress and anxiety in adults
US6726133B2 (en) * 1997-07-18 2004-04-27 Pulsewave Llc Process for micronizing materials
WO1999025331A1 (en) * 1997-11-13 1999-05-27 University Of Florida Use of ketoacids together with amino acids for enhancing muscle performance and recovery from fatigue
US5955107A (en) 1997-12-12 1999-09-21 Fmc Corporation Pharmaceutical suspension tablet compositions
US6905707B2 (en) * 1998-05-28 2005-06-14 Medical Research Institute Controlled release arginine alpha ketoglutarate
US6136339A (en) * 1998-08-21 2000-10-24 Gardiner; Paul T. Food supplements and methods comprising lipoic acid and creatine
CA2246014C (en) * 1998-08-21 2001-12-11 Paul T. Gardiner Food supplements and methods comprising lipoic acid and creatine
US6599530B2 (en) 1998-09-14 2003-07-29 Orion Corporation Oral compacted composition comprising catechol derivatives
FR2789997B1 (en) * 1999-02-18 2004-12-03 Rhodia Chimie Sa COMPOSITION COMPRISING AN OIL IN WATER EMULSION AND AN INORGANIC AGENT
US6383527B1 (en) 1999-03-04 2002-05-07 Nps Pharmaceuticals, Inc. Compositions comprising valerian extracts, isovaleric acid or derivatives thereof with a NSAID
US6245352B1 (en) 1999-04-27 2001-06-12 Eli Lilly And Company Pharmaceutical formulation
US9486429B2 (en) * 1999-06-01 2016-11-08 Vanderbilt University Therapeutic methods employing nitric oxide precursors
US6653352B2 (en) * 1999-09-29 2003-11-25 Medical Merchandising, Inc. Pain reliever and method of use
US6312736B1 (en) 1999-12-09 2001-11-06 Biotech Corporation Herbal composition to relieve pain
US20010041675A1 (en) * 2000-01-24 2001-11-15 Jacobs Robert H. Satisfy composition and method of weight control
WO2003030868A1 (en) * 2001-10-09 2003-04-17 Bristol-Myers Squibb Company Flashmelt oral dosage formulation
US6399116B1 (en) * 2000-04-28 2002-06-04 Rulin Xiu Rhodiola and used thereof
DE60133270T2 (en) * 2000-05-10 2009-04-23 Jagotec Ag CRUSHING BY MEANS OF GRINDING BODY
US6277396B1 (en) * 2000-05-11 2001-08-21 Maximum Human Performance, Inc. Dietary supplement containing a thermogenic substance and an adrenal support substance
CN100457090C (en) * 2000-08-31 2009-02-04 斯凯伊药品加拿大公司 Milled particles
AUPR177300A0 (en) * 2000-11-29 2000-12-21 Centre For Molecular Biology And Medicine Therapeutic methods
US7049283B2 (en) 2000-12-06 2006-05-23 Novartis Ag Pharmaceutical compositions for the oral delivery of pharmacologically active agents
JP2002371003A (en) * 2001-06-15 2002-12-26 Kikkoman Corp Inhibitor against blood sugar level increase
US20030013639A1 (en) * 2001-07-03 2003-01-16 Lisa Yurchak Sleep inducing antacid composition
DE60221421T2 (en) 2001-09-17 2008-05-21 Phytos Inc., San Anselmo STANDARDIZED EXTRACTS OF SCUTELLARIA LATERIFLORA
US6579543B1 (en) * 2002-02-22 2003-06-17 Jackie H. McClung Composition for topical application to skin
DE10208335A1 (en) * 2002-02-27 2003-09-04 Roehm Gmbh Pharmaceutical form and process for its preparation
US20050163857A1 (en) * 2002-04-03 2005-07-28 Ashok Rampal Clarithromycin formulations having improved bioavailability
US6903136B2 (en) * 2002-04-22 2005-06-07 Experimental And Applied Sciences, Inc. Food supplements containing 4-hydroxyisoleucine and creatine
US20030232091A1 (en) * 2002-06-17 2003-12-18 Adi Shefer Stabilized retinol for cosmetic dermatological, and pharmaceutical compositions, and use thereof
US20040005368A1 (en) * 2002-07-01 2004-01-08 Morris Mann Novel approach to weight loss comprising a modified protein composition that regulates blood sugar in conjunction with compositions that increase oxygen uptake and suppress appetite
US7625362B2 (en) * 2003-09-16 2009-12-01 Boehringer Technologies, L.P. Apparatus and method for suction-assisted wound healing
US6703412B1 (en) 2002-09-27 2004-03-09 Holly A. Rosenthal Method of treating sleeplessness with melatonin on an acute basis
DK1569680T3 (en) * 2002-10-22 2009-05-18 Waratah Pharmaceuticals Inc Treatment of diabetes
WO2004037203A2 (en) * 2002-10-24 2004-05-06 Enos Pharmaceuticals, Inc. Sustained release l-arginine formulations and methods of manufacture and use
US6946151B2 (en) * 2002-11-12 2005-09-20 Ayurvedic-Life International, Llc Therapeutic compositions
US20040247699A1 (en) * 2002-12-20 2004-12-09 Bernardina Johanna Martina Delsing Method for the prevention or treatment of overweight in mammals
JP2004217532A (en) * 2003-01-10 2004-08-05 Maruzen Pharmaceut Co Ltd Mulberry leaf extract and method for producing the same, and anti-hyperglycemic composition and obesity-preventing composition
JP2006523620A (en) * 2003-02-19 2006-10-19 バイオヴェイル ラボラトリーズ インコーポレイテッド Rapid absorption selective 5-HT agent formulation
US8512727B2 (en) * 2003-03-03 2013-08-20 Alkermes Pharma Ireland Limited Nanoparticulate meloxicam formulations
US7129273B2 (en) * 2003-04-30 2006-10-31 Creative Compounds, Llc Dicreatine Malate
CN1257259C (en) * 2003-06-21 2006-05-24 陈豪锋 Formulation for health-care red rice wine
EP1686976A2 (en) * 2003-11-05 2006-08-09 Santarus, Inc. Combination of proton pump inhibitor and sleep aid
CA2544627A1 (en) * 2003-11-05 2005-05-19 Elan Pharma International Ltd. Nanoparticulate compositions having a peptide as a surface stabilizer
DE10352822A1 (en) * 2003-11-12 2005-06-23 Bioghurt Biogarde Gmbh & Co. Kg Use of an additionally fermented cereal sludge for the prevention and / or treatment of elevated blood sugar levels
US8337915B2 (en) * 2004-01-10 2012-12-25 S George Aburdeineh Fenugreek seed extract to lower blood cholesterol
US20050209148A1 (en) * 2004-02-20 2005-09-22 Arnon Rosenthal Methods of treating obesity or diabetes using NT-4/5
DE102004008804A1 (en) * 2004-02-20 2005-09-08 Boehringer Ingelheim Pharma Gmbh & Co. Kg Multilayer tablet
CA2556753C (en) * 2004-02-20 2014-11-25 Lifescape Biosciences Incorporated Compositions and methods for sleep regulation
DE102004009962A1 (en) * 2004-03-01 2005-09-22 Degussa Ag Use of guanidine compounds as physiological restorative in the form of nutritional supplements, feed additives, in cosmetic preparations and as plant strengthening agents
DE602005023003D1 (en) 2004-04-06 2010-09-30 Taiyokagaku Co Ltd USE OF A COMBINATION OF THEANINE AND SEROTONIN AGAINST SLEEP DISORDER
CN1568803A (en) * 2004-04-30 2005-01-26 南阳市海达生物技术有限公司 Food with blood-sugar/blood-fat reducing function and preparation method thereof
US20050249843A1 (en) * 2004-05-07 2005-11-10 Loren Wallis Low carbohydrate caramel corn composition
US20050282870A1 (en) * 2004-06-16 2005-12-22 Carter Stephen G Peripherally-acting vasodilators
DE102004036047A1 (en) * 2004-07-24 2006-02-23 Bioghurt Biogarde Gmbh & Co. Kg Physiologically active composition
CN101048179A (en) * 2004-08-25 2007-10-03 Mtor配方设计公司 Compositions and methods for activating protein synthesis and deactivating catabolic processes in skeletal muscle
WO2006034586A1 (en) * 2004-09-29 2006-04-06 Aplodan Formulations Ltd. Nutritional composition for promoting muscle performance and acting as hydrogen (h+) blocker
WO2006108295A1 (en) * 2005-04-11 2006-10-19 New Cell Formulations Ltd. Supplemental dietary composition for increasing muscle size and strength
CA2516678A1 (en) * 2005-08-18 2007-02-18 Gakic Formulations Ltd. Supplemental dietary composition for enhancing muscle performance and/or recovery from fatigue

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6869622B2 (en) * 1999-07-21 2005-03-22 Ancile Pharmaceuticals, Inc. Composition for improving sleep quality and efficiency, and methods of preparing and using the composition
US20050129783A1 (en) * 2001-04-19 2005-06-16 Mccleary Edward L. Composition and method for treatment of neurophysiological conditions and maintenance of neurophysiological health
US20040234544A1 (en) * 2001-08-09 2004-11-25 Ralf Jager Formulation containing (lyso-)phosphatidylserine for the prevention and treatment of stress states in warm blooded animals
US6770263B1 (en) * 2001-10-01 2004-08-03 Naturewell, Incorporated Compositions and methods for the treatment of aches and pains

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
AWAD R. ET AL.: "Phytochemical and biological analysis of Skullcap (Scutellaria lateriflora L.): A medicinal plant with anxiolytic properties", PHYTOMEDICINE, vol. 10, 2003, pages 640 - 649, XP004957183 *
BALDWIN C.M. ET AL.: "Antioxidant nutrient intake and supplements as potential moderators of cognitive decline and cardiovascular disease in obstructive sleep apnea", SLEEP MEDICINE REVIEWS, vol. 9, December 2005 (2005-12-01), pages 459 - 476, XP005156893 *
DOLLINS A.B. ET AL.: "Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance", PROC. NATL. ACAD. SCI. USA, vol. 91, March 1994 (1994-03-01), pages 1824 - 1828, XP008124255 *
FOSSEL A. ET AL.: "Effect of a fixed valerian-hop extract combination (Ze 91019) on sleep polygraph in patients with non-organic insomnia: a pilot study", EUROPEAN JOURNAL OF MEDICAL RESEARCH, vol. 5, 18 September 2000 (2000-09-18), pages 385 - 390, XP001106917 *
KENNEDY D.O. ET AL.: "Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm)", PHARMACOLOGY, BIOCHEMISTRY, AND BEHAVIOR, vol. 72, 2002, pages 953 - 964, XP008124256 *
LIS-BALCHIN M. ET AL.: "Studies on the mode of action of the essential oil of lavender (Lavendula angustifolia P. Miller)", PHYTOTHERAPY RESEARCH, vol. 13, 1999, pages 540 - 542, XP002581357 *
See also references of EP1991241A4 *
SOULIMANI R. ET AL.: "Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavenoid derivatives and maltol in the mouse", JOURNAL OF ETHNOPHARMACOLOGY, vol. 57, 1997, pages 11 - 20, XP003012520 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010215561A (en) * 2009-03-17 2010-09-30 Shiseido Co Ltd Circadian rhythm-adjusting agent
WO2012112116A1 (en) * 2011-02-16 2012-08-23 Wellbemed Sweden Ab Foodstuff comprising an extract mixture
CN103476274A (en) * 2011-04-18 2013-12-25 雀巢产品技术援助有限公司 Nutritional compositions having alpha-hica and alpha-ketoglutarate

Also Published As

Publication number Publication date
US20090011015A1 (en) 2009-01-08
JP2009527504A (en) 2009-07-30
US20070196348A1 (en) 2007-08-23
US20070202165A1 (en) 2007-08-30
US20070196508A1 (en) 2007-08-23
EP1991241A1 (en) 2008-11-19
US7906154B2 (en) 2011-03-15
EP1996199A4 (en) 2009-07-15
CA2560107C (en) 2016-03-29
US7794749B2 (en) 2010-09-14
US7749547B2 (en) 2010-07-06
CA2560107A1 (en) 2007-08-23
EP1991241A4 (en) 2009-07-08
CA2556305C (en) 2013-08-06
WO2007095717A1 (en) 2007-08-30
US7476405B2 (en) 2009-01-13
WO2007095733A1 (en) 2007-08-30
US20070196470A1 (en) 2007-08-23
US20070202166A1 (en) 2007-08-30
CA2642761A1 (en) 2007-08-30
ZA200807489B (en) 2009-11-25
WO2007095734A1 (en) 2007-08-30
US20090142410A1 (en) 2009-06-04
US20070264337A1 (en) 2007-11-15
AU2006338840A1 (en) 2007-08-30
CA2556305A1 (en) 2007-08-23
US7914826B2 (en) 2011-03-29
AU2006338839A1 (en) 2007-08-30
WO2007095718A1 (en) 2007-08-30
EP1996199A1 (en) 2008-12-03

Similar Documents

Publication Publication Date Title
US7914826B2 (en) Method for promoting sleep
US10512614B2 (en) Compositions comprising a cannabinoid and spilanthol
US7455864B2 (en) Melatonin-based composition for improved sleep
US9375463B2 (en) Compositions and methods for improving sleep using a nutraceutical formulation
Galeotti et al. St. John's Wort seed and feverfew flower extracts relieve painful diabetic neuropathy in a rat model of diabetes
Lanje et al. Medicinal natural drug of Valerian (Valerina Officinalis): an-over review
Kim et al. Herbs for the treatment of insomnia
JPWO2015076286A1 (en) Ephedrine alkaloid-removed Mao extract, its production and use
Olatunji et al. Sceletium tortuosum: a review on its phytochemistry, pharmacokinetics, biological and clinical activities
Bartels et al. Herbal and related remedies
TW201618802A (en) Natural extracts for modulating PP2A methylation, and providing antioxidant and anti inflammatory activity
Olatunji et al. Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological, pre-clinical and clinical activities
Rios et al. Evidenced-based use of botanicals, minerals, and vitamins in the prophylactic treatment of migraines
EP3142668B1 (en) A formulation for ameliorating premature ejaculation
Ghaderi et al. The effect of cinnamon zeylanicum essential oil on treatment of patients with unipolar nonpsychotic major depressive disorder treated with fluoxetine
Balch et al. Prescription for Drug Alternatives: All-Natural Options for Better Health without the Side Effects
KR100561251B1 (en) Composition comprising the extract of Glycine max having monoamine oxidase-inhibiting activity
Poursaleh et al. A review of available herbal medicine options for the treatment of chronic insomnia
KR20160045256A (en) A composition comprising an extract of Hippophae rhamnoides for treating or preventing a physiological stress, depression or dementia
Cicero et al. Nutraceuticals Active on Central Nervous System
JP2024526109A (en) Compositions for promoting restful sleep and methods of making and using same
BR102021024155A2 (en) USE OF A SOLUTION/EMULSION FROM ZIZIPHUS COTINIFOLIA REISSEK IN THE TREATMENT OF ANXIETY DISORDERS
WO2008122723A2 (en) Use of poly-unsaturated fatty acids and flavonoids as active ingredients in a composition for preventing and/or treating migraines
Koetter Valerian and hops: Synergy, mode of action, and clinical evidence
Sarropoulou Benecial Effects of Serotonin and Melatonin on Cancer, Neurodegenerative Diseases, and Related Disorders in Humans

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
DPE1 Request for preliminary examination filed after expiration of 19th month from priority date (pct application filed from 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2008555578

Country of ref document: JP

Ref document number: 2642761

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2006338839

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2006761118

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2006338839

Country of ref document: AU

Date of ref document: 20060714

Kind code of ref document: A